INTRODUCTION:

Camels are recognized for a variety of reasons, including their economic importance. According to the FAO, there are 19 million of these creatures in the world, with four million in Asia and 15 million in Africa. There are around 17 million dromedaries and 2 million two-humped camels in the world¹. Iraq has an estimated total of 58,293 camels. Camels can be used for a large selection of tasks, and their productivity is high. Desertification, climate change, and shortages in food and water are becoming more common in an era when these concerns are growing more widespread, and camels can challenge such difficult circumstances.

Camel milk might be a good source of nutrients and water in these situations².

Camel milk has a long history of therapeutic use in numerous cultures due to the constituents' medicinal properties, including vitamins, particularly the high quantities of vitamin C in camel milk². Various studies reported the effective uses of camel milkforthe treatment a variety of illnesses, such as jaundice, malaria, digestive disturbances, pneumonia, and tuberculosis. This is understandable as a result of the inclusion of several beneficial nutritional and medicinal components. The milk of camels, for example, may be a factor in modulating the levels of insulin in patients with type 2 diabetic mellitus (T2DM)³.

Male fertility in animals and humans has been negatively affected by contact with environmental toxins, and this is a major factor in the decline of sperm effectiveness and quantity^4-6. Reproductive health reduction could be affected by a variety of factors, including air pollution, harmful substances in the workplace, medicines, and dietary additives^7,8.

Aflatoxins (AF) are critical mycotoxins produced mainly by Aspergillusflavus and Aspergillusparasiticus on a range of foods under suitable environments and are particularly destructive to humans and animals⁹. B1, B2, G1 and G2 are the most common types of AFs, with AFB1 being the most hazardous to human beings and animals¹⁰.

It was found that utilization of herbal extracted compounds, vitamins such as vitamin C and E, and Co-enzyme Q10 play roles as hepatoprotective^11-14, nephroprotective¹⁵, and genitoprotective^16,17 agents. Aflatoxin can be found in Raw Peanut¹⁸, and it was found that the liver contributes to the production of AflatoxinB1 as a result of Aflatoxicosis¹⁹.

There is no data on the effects of aflatoxin on spermatogenesis and steroidogenesis. Hints taken from female experiments on the influence of different mycotoxins on steroidogenesis depict the biological danger that mycotoxins can pose. In rats, they decreased the weight of male genital organs, reduced spermatid and testosterone levels^20,21, degeneration of the Sertoli cells and increased apoptosis and the viability of the cells²². Aflatoxins can affect Leydig cells directly, affecting their enzymatic and hormonal functions by decreasing testosterone secretion in a dose-reliant manner, inhibiting the expression of certain dehydrogenase enzymes, and mRNA production but it is unclear if this translates into anything substantive²³.

The present study aims to determine the toxicological side effects of aflatoxin B1 on the testis, epididymis, liver, and kidneys of adult male rats, and to examine the possible role of camel milk, as a natural antidote, in ameliorating these effects.

MATERIALS AND METHODS:

Aflatoxin B1:

AFs (Sigma Aldrich, USA) has been used in the dose of 0.3mg/kg BW/day²⁴.

Camel milk:

Cm was obtained fresh from a camel breeder in Al-Hamza district in Al-Diwaneyah city. It was transported in a cool box.

Animal ethics and care:

For this experiment, all animals were handled in accordance with international and national animal welfare standards. A total of 120 adult male rats (aged at 90 days and weighted 170±3.8g) were adapted to the animal house environment before the start of the experimental procedures. A room of proper ventilation, temperature at 22±2ºC, and light:dark (12:12). Ad libitum standard chow and water was utilized to hosted the rats.

Experimental design:

The male rats were allocated to four equal groups at random (30 each). Control (C) group received distilled water orally, Cm group received camel milk (10ml/kg BW/day), Af group received AfB1 (0.3mg/kg BW/day), and CmAf group received a combination of camel milk and AfB1. After 21 and 42 days of treatment, 10 males from each group (for each period) were weighted, anesthetized, euthanized, and the testis, epididymis, prostates, and seminal vesicles were dislocated and weighted to calculate their relative weights (g/100 BW). Sample tissues from testis, epididymis, liver, and kidneys were also obtained and fixed in formalin buffer solution for histopathological examination.

Histological slide preparation:

The microscopic slides were prepared at 5µM of thickness and hematoxylin-eosin-stained according to Bilinska et al.²⁵.

Statistical analysis:

GraphPad Prism V5 (USA) with the use of M±SD to display the data was utilized. Significant data (at P<0.05) based on the use of one-way ANOVA (Newman- Keuls) were calculated (for each time point) between groups, while Significant data (at P<0.05) based on the employment of student t-test were measured (for each group) between time points²⁶.

RESULTS:

Body weight changes:

Body weights of aflatoxin-B1 treated male rats (Af group) decreased significantly (p˂0.05) than control and camel milk treated (Cm group) male rats. However, a combination treatment of camel milk and aflatoxin-B1 (AfCm group) showed restored body weight, but still lower significantly (p˂0.05) as compared with control and Cm groups (Table 1). When comparing the two periods, all experimental groups recorded significant (p˂0.05) increase at second stage except Af group which decreased significantly (p˂0.05).

Relative weight for genital organs:

In comparison with control male rats, the relative weight of testes, epididymis, seminal vesicle, and Prostate of Cm group male rats significantly increased (p˂0.05) and that of Af group male rats significantly decreased (p˂0.05) whereas a combination treatment group (AfCm) revealed insignificant difference (p>0.05) at 21 day period but significantly (p˂0.05) decreased at 42 day period. When comparing the two periods of the study, control, Cm, and AfCm groups recorded significant increase (p˂0.05) at 42 day period in comparison with 21 day period, whereas Af group recorded further significant decrease (p˂0.05) at 42 day period than 21 day period (Table 1).

Histopathological changes:

Testes:

Testes histological findings of control (C) and CM group male rats dominated the entirely typical structure of the germinal epithelium in the seminiferous tubules and interstitial tissues, which showed active spermatogenesis and consisted of a regular arrangement of all forms of germ cells and Sertoli cells (Figures 1-C21 and Cm21). The sections of Af group male rats revealed a decline of germ cells number, germ cell layers and spermatogenesis arrest (Figures 1-Af21), as several seminiferous tubules showed germ cell disorganization or exfoliation and increased vacuoles inside the germ epithelium. InAfCm group male rats, the testicular architecture was improved compared with that of the Af group, as substantial reduction in the degree of germ epithelium degeneration was observed in AfCm group. Even if the germ epithelium had not wholly recovered in all seminiferous tubules, several tubules were recovered, and the germ cells were well organized(Figures 1-AfCm21).

At day 42 of the experiment, the testes of control (Figures 1-C42), CM group (Figures 1-Cm42) male rats showed normal histological architectures. In contrast, the Af group male rats revealed micro and macrovacuolation of the seminiferous tubule (Figures 1-Af42). Vacuoles were found within or between Sertoli cells in most sections, and they could contain fluid, lipid, or reflect dilatation of the endoplasmic reticulum or intercellular gaps. Furthermore, the vacuoles were associated with global germinal cell degeneration and atrophy. Congestion of blood vessels were also detected. Sections from AfCm group (Figures 1-AfCm42) male rat testes showed normal seminiferous tubules epithelia, cell population within the tubule, and lumen, where active spermatogenesis and regular arrangement of all forms of germ cells and Sertoli cells were observed.

Figure (1): Sections of the seminiferous tubules obtained from control (C), camel milk treated (Cm), aflatoxin treated (Af), and combination treated (AfCm) male rats at day 21 and 42 of the experiment. C-21: shows normal seminiferous tubule epithelium, cell population within the tubule, and lumen (L), as well as the interlobular compartment (IC). Cm-21: shows the normal spermatogenic cycles with normal spermatogonialcharecteristics (SG) that rest upon the basal lamina (BM), spermatocytes (SP), spermatids (Sd), elongated spermatids (ES) and interstitial cells (IC). Af-21: Shows seminiferous tubular atrophy (A), a decline of germ cells number, and spermatogenous arrest (black arrow), and destruction of basal lamina (yellow arrows). AfCm-21: shows normal seminiferous tubule epithelium, cell population within the tubule, and lumen (L), as well as the interlobular compartment (IC), normal spermatogonialfeachers (SG), spermatocytes (SP), spermatids (Sd), elongated spermatids (ES) and interstitial cells (IC). The Spermatogonia (Sg) rest upon the basal lamina. C-42: shows normal seminiferous tubule epithelium, cell population within the tubule, and lumen (L), as well as the interlobular compartment (IC). Cm-42: shows normal histoarchitecture of testes with normal spermatogonialcharecteristics (SG) that rest on the basal lamina, spermatocytes (SP), spermatids (Sd), elongated spermatids and interstitial cells. Af-42: shows an increase of interstitial space (yellow arrows), severe atrophy and complete destruction of seminiferous tubules (stars), loss of all germinal epithelial cells and eosinophilic exudate was evident. AfCm-42: shows normal histoarchitecture of testes with normal seminiferous tubule epithelium, cell population within the tubule, and lumen. H&E, 400X.

Liver:

At day 21 of the experiment, normal liver structures were noticed in the sections of control (Figure 2-C21) and CM group (Figures 2Cm21) male rats. In Af group male rats, the liver sections showed definite lesions (Figures 2-Af21), such as necrosis of hepatocytes, deposition of eosinophilic exudate with profuse oedema, hepatocytes showed vacuolar degeneration with tiny and large droplets, hydropic degeneration, local hyperemia, considerable sinusoidal contraction, and pyknotic nuclei of some hepatocytes, as well as extravasated RBCs. Although most liver parenchyma seems to be normal in AfCM male rats, but some histopathological changes were noticed, including infiltration of some inflammatory cells near the portal vein and hepatic sinusoidal dilatation (Figures 2-AfCm21).

At day 42 of the experiment, also no specific lesions were observed in liver tissues of control (Figures 2-C42) and CM group (Figures 2-Cm42) male rats. In the Af male rats liver sections, a vacuolar and massive hydropic degeneration, and a focal area of hepatocytes necrosis were noticed as well as marked sinusoidal dilatation and many hepatocytes with pyknotic nuclei (Figure 2-Af42). Liver sections from AfCM group male rats showed normal hepatocytes radiated from the central vein, but at the same time other examined sections showed enlarged portal veins engorgement with eosinophilic material, and necrosis of some hepatocytes. (Figures 2-AfCm42).

Figure (2): Sections of the livers obtained from control (C), camel milk treated (Cm), aflatoxin treated (Af), and combination treated (AfCm) male rats at day 21and 42 of the experiment. C-21: shows cords of normal hepatocytes radiated from central vein. Cm-21: shows cords of normal hepatocytes radiated from central vein. Af-21: shows severe necrosis of hepatocytes (N), deposition of eosinophils exudate (E), and extra-vassated RBCs (H) and infiltration of lymphocytes (L) were clearly obvious. AfCm-21: shows normally radiated hepatocytes cords, infiltration of some inflammatory cells (yellow arrows) near the portal vein, and hepatic sinusoidal dilatation. C-42: shows normal liver texture. Cm-42: shows cords of normal hepatocytes radiated from central vein. Af-42: shows focal area of degeneration and necrosis of the hepatocytes, the pyknosis of the nucleus of the hepatocytes (yellow arrows) was evident and hepatic sinusoidal dilatation. AfCm-42: shows normally radiated hepatocytes cords, infiltration of some inflammatory cells (yellow arrows) near the dilated portal vein, hepatic sinusoidal dilatation and presence of exudate. H&E, 100X.

Kidneys

At day 21 of the experiment, the histopathological sections from kidneys of CM group males showed normal glomeruli, but there is a deposition of eosinophilic exudate in the proximal tubule’s lumen (Figures 3-Cm21). In comparison, Af group males, revealed necrosis of the glomeruli, moderate parenchymatous tubular degeneration, predominantly in the distal tubules, and deposition of eosinophilic exudate in the proximal and distal tubule's lumen (Figures 3-Af21). Hydropic and vacuolar degeneration was also noticed, but the severe degree characterized by tubular epithelial cells' desquamation in almost all cells. In the same context, AfCM male rats showed normal glomeruli, but some of the proximal tubules are suffering from sloughing, and some of the distal tubules are engorged with eosinophilic materials (Figures 3-AfCm21).

Histological sections obtained at day 42 of the experiment from CM group male rats (Figures 3-Cm42) showed normal architecture of kidneys, whereas those obtained from Af group males revealed complete destruction of the glomeruli, as well as the presence of interstitial nephritis characterized by engorgement of blood vessels and severe infiltration of inflammatory cells (Figures 3-Af42). Like CM group, AfCM group male rats showed normal glomeruli and renal tubules (Figures 3-AfCm42).

Figure (3): Sections of the kidneys obtained from camel milk treated (Cm), aflatoxin treated (Af), and combination treated (AfCm) male rats at day 21 and 42 of the experiment. C-21: shows normal glomeruli and renal tubules (proximal and distal). Cm-21: shows normal glomeruli, but there is a deposition of eosinophilic exudate in the lumen of the proximal tubule (yellow arrow). Af-21: shows necrosis of the glomeruli (yellow arrows), sloughing of the epithelial layer of the renal tubules (black arrow), thickening of the wall of the renal tubules and deposition of eosinophil exudate (blue arrow).AfCm-21: shows normal glomeruli (yellow arrows), but some of the renal tubules suffering from sloughing (blue arrow), and some others are engorged with eosinophilic materials (white arrows), also congested blood vessel was evident. Cm-42: shows normal glomeruli and renal tubules (proximal and distal tubules). Af-42: shows shows necrosis of the glomeruli (yellow arrow), complete destruction of some glomeruli, extravassated RBCs and engorgement of renal tubules (white arrows). AfCm-42: shows normal glomeruli and renal tubules (proximal and distal). H&E, 100X.

Epididymis:

At day 21 of the experiment, normal histological appearance of the epididymis were noticed in the CM group (Figures 4-Cm21) male rats, while Af group males showed epithelial hyperplasia, epithelial cytoplasmic vacuolation, and the depletion of sperms from the epididymis' lumen (Figures 4-Af21). Like the control and CM groups, the AfCm group male rats revealed normal, stereocilia with a presence of sperms in the lumen, but Some ductules were devoid of spermatozoa in addition to sloughed germ cells in this group(Figures 3-AfCm21).

At day 42 of the experiment, the epididymis tissue of CM group male rats (Figures 4-Cm42), revealed normal pseudostratified columnar epithelium, stereocilia with sperms in the lumen. Af group male rats showed degeneration and detachment of epithelial layer, epithelial hyperplasia, epithelial cytoplasmic vacuolation, and depletion of sperms in the lumen (Figures 4-Af42). Most of AfCM group males revealed normal pseudostratified columnar epithelium, stereocilia with sperms in the lumen (Figures 4-AfCm42), but other sections revealed degeneration and detachment of epithelial layer, epithelial cytoplasmic vacuolation, and depletion of sperms in the lumen.

Figure (4): Sections of the epididymis obtained from camel milk treated (Cm), aflatoxin treated (Af), and combination treated (AfCm) male rats at day 21 and 42 of the experiment. C-21: shows normal pseudostratified columnar epithelium (black arrow), stereocilia with sperms in the lumen (yellow arrow). Cm-21: shows normal pseudostratified columnar epithelium, stereocilia with sperms in the lumen. Af-21: shows depletion of sperms (yellow arrow) from the lumen of the epididymis can also be noticed, mild degeneration of columnar epithelium (yellow arrow), vacuolation of principal cells (black arrows). AfCm-21: shows normal pseudostratified columnar epithelium, stereocilia with sperms in the lumen, and some ductules of the epididymis were devoid of spermatozoa (stars) in addition to sloughed germ cells (arrows). Cm-42: shows normal pseudostratified columnar epithelium (yellow arrows), stereocilia (white arrow) with sperms (S) in the lumen. Af-42: shows degeneration and detachment of epithelial layer (white arrow), epithelial cytoplasmic vacuolation (yellow arrows), as well as depletion of sperms in the lumen (black arrow). AfCm-42: demonstrated giant cells (white arrows) and sloughed germ cells in the lumina, and Some degeneration and detachment of epithelial layer. H&E, 400X.

DISCUSSION:

Body weight and relative weight of genital organs:

The AF B1 affected male rats (Af group) showed reduction in body weight gain. This finding agrees with those reported by Supriya et al. ²⁷. This could be related to decreased feed intake, as AFB1 has been demonstrated to decrease the expression of orexigenic and anorexigenic hypothalamic neuropeptides, which control feed intake, resulting in a reduction in body weight gain ²⁸. It is well-known that AF disrupts the function of thymus glands, which is related with the low feed intake and body weight gain ²⁹, and that is why our animals suffered loss of appetite due to the effects of AF. As well as to the restricting of food absorption, various mechanisms by which AFB1 might limit animal to keep normal or gain weight, such as: alterations in gastrointestinal tract function that hinder normal nutrition absorption and consumption, a rise in vulnerability to other diseases that affect development might be caused by the immunosuppressive impact of AFB1, carbohydrate and lipid metabolic alterations produced by AFB1, as well as AFB1-mediated downregulation of insulin-like growth factor genes ³⁰.

When CM was utilized in combination with AFB1, rises in the body weight of male rats was demonstrated. This could be due to improvements in the intestine welfare enhanced by the use of CM. Lactoferrin and immunoglobulins are the principal active elements in CM from a medical standpoint, where various investigations mentioned that camel lactoferrin possess a wide range of beneficial qualities ³¹. Gastrointestinal infections occurred accompanied with AFB1 toxicity are highly common due to the effects of immune suppression by AF. CM suppresses and neutralizes the effects of AF from different microorganisms ³². Our results agree with those by Muleta et al. ³³, who detected that using CM in children in areas with less food resources had a noticeable impact in improving growth in the tested children in Somali and Ethiopia. When comparing the time-periods of the AFB1 combination with the CM, we noticed that the effect of CM was highly pronounced as the more increases in the weight of male rats were recorded. This might be as results that the milk emphasized more beneficial actions as the time went on.

In the current work, we noticed decreases in the testicular, epididymal, seminal vesicle, and prostate relative weight. This could be a typical effect of AF on the examined animals. Our results came in agreements with those reported by Supriya et al. ²⁷, who detected decreases in the weight of these organs. Degeneration of the germinal epithelium may be the cause of the testicular weight loss. The reduction in sperm output might explain the weight reduction in the epididymis. Other researchers have identified comparable outcomes in male rats subjected to AFB1, which may be attributable to the decreased bioavailability or synthesis of androgens in the AFB1-expesed animals^34,35.

When the CM was used in the combined group with AF, improvements in the weight of genital organs were recorded. From the aspect of anti-inflammatory effect, CM has lactoferrin and proteins that help in the regeneration of the damaged genital tissues, which may enhance sperm production and regaining the normal weight of these organs. El-Sawy et al. ³⁶ have found that after using monosodium glutamate in male rats, the genital organ features of these animals suffered down-regulation and weight loss. Also, they found that glutathione level, as an important antioxidant, was restored after using CM, indicating fresh epithelial regeneration of these organs.

Histopathological changes:

The observed significant testicular lesions induced by AF B1 were in agreement with those reported by Owumi et al. ³⁷, who found vacuolation and a prolonged region of tubular necrosis of the seminiferous tubules with insufficient sperm in the lumens of testes of male rats. These changes were reported to be reversed by the use of CM as documented by Mohamed et al. ³⁸, who found that the toxic effects of fenpropathrin was eliminated by the use of CM, as it stop the activity of apoptosis via caspase 3 and P53 pathways, which is important in the tissue repair of the testes and other organs, and this completely agrees our findings regarding this part of the results. The liver microscopic picture was altered due to the effect of AF B1 in the male rats. AF hepatotoxicity is primarily caused by the production of ROS and the resulting in peroxidative injury, lipid peroxidation, and the synthesis of 8-hydroxydeoxyguanosine ³⁹.

Our results showed significant effects of CM in reversing these alterations. Korish and Arafah ⁴⁰ found that CM consumption for eight weeks lowered hepatic fat buildup and the infiltration of inflammatory cells, restored liver performance, raised the GSH contents, and improved the alterations in the lipid profile in rats treated with high cholesterol diet. Moreover, Zuberu et al. ⁴¹ showed that liver fatty change in male rats treated with poloxamer 407, a widely used component in mouthwashes and deodorants, and other hygiene care products, was lowered with the use of CM.

The results showed several changes in the kidney due to the effects of AF B1. These findings agree with Li et al. ⁴². These changes were reversed after using CM in a combination with AF B1, suggesting preferable effects of CM in treating these histopathological. Al-Asmari et al. ⁴³ found that the degeneration and necrosis in the glomeruli and tubules were reversed after using CM to treat these drastic effects induced by gentamicin. In our study, these alterations were converted to close to normal status after using CM as an effector against AF B1 effects; however, low grades of degeneration and necrosis can still be seen in the tubules of the affected kidneys.

CONCLUSION:

According to the current study, male rats exposed to AFB1 were extremely toxic. Losses in body weight and the relative weight of the genital organs are recorded. Additionally, this mycotoxin damages the liver and kidneys in addition to the genital organs, resulting in testicular, epididymal, hepatic, and renal histopathological abnormalities. According to the current results, camel milk may aid in regaining body and organ weights and ameliorating histological lesions.

REFERENCES:

1. Galali Y. Al-Dmoor HM. Miraculous Properties of Camel Milk and Perspective of Modern Science. J Fam Med Dis Prev. 2019;5(1):1–7. DOI: 10.23937/2469-5793/1510095

2. Ali A. Baby B.Vijayan R. From desert to medicine: A review of camel genomics and therapeutic products. Front Genet. 2019; 10(2):1–20. DOI: 10.3389/fgene.2019.00017.

3. Mirmiran P.Ejtahed HS.Angoorani P.Eslami F.Azizi F. Camel milk has beneficial effects on diabetes mellitus: A systematic review. Int J EndocrinolMetab. 2017;15(2):42150. DOI: 10.5812/ijem.42150.

4. Aitken RJ.Koopman P. Lewis SEM. Seeds of concern. Nature 2004;432(7013):48–52. DOI: 10.1038/432048a.

5. Swan SH. Elkin EP.Fenster L. The question of declining sperm density revisited: An analysis of 101 studies published 1934-1996. Environ Health Perspect 2000; 108(10):961–6. http://ehpnet1.niehs.nih.gov/docs/2000/108p961-966swan/abstract.html.

6. Shenuka S.Thiyagarajan T.Sambath Kumar R. A Review on the Effect of Immunosuppressants on Fertility. Research J. Pharm. and Tech. 2019; 12(3): 1441-1447.DOI: 10.5958/0974-360X.2019.00239.7.

7. Herath CB. Jin W. Watanabe G.et al. Adverse effects of environmental toxicants, octylphenol and bisphenol A, on male reproductive functions in pubertal rats. Endocrine 2004; 25(2):163–72. DOI:10.1385/ENDO:25:2:163.

8. Sharpe RM. Lifestyle and environmental contribution to male infertility. Br Med Bull. 2000;56(3):630–42. DOI: 10.1258/0007142001903436.

9. Alnaemi HS. Estimation of Aflatoxin M1 Levels in Some Dairy Products Manufactured from Raw Milk Experimentally Inoculated with Toxin. Iraqi J Vet Med. 2019;43(1):50–8. DOI:10.30539/iraqijvm.v43i1.471.

10. Marijani E.Charo-Karisa H.Gnonlonfin GJB. Et al. Effects of aflatoxin B1 on reproductive performance of farmed Nile tilapia. Int J Vet Sci Med. 2019;7(1):35–42. DOI: 10.1080/23144599.2019.1678315.

11. Parveen A. Singh A.Rajendiran A. et al. Herbal elicited Hepatoprotection and Hepatotoxicity – A Comprehensive Review. Asian J. Pharm. Res. 2022; 12(2):155-1.DOI: 10.52711/2231-5691.2022.00024.

12. Rathore P.Rao SP. Roy A. et al. Hepatoprotective Activity of Isolated Herbal Compounds. Research J. Pharm. and Tech. 2014; 7(2): 229-234.

13. Jwad SM. Abbas B.Jaffat HS. Study of The Protective Effect of Vitamin C plus E on Lincomycin-Induced Hepatotoxicity and Nephrotoxicity. Research J. Pharm. and Tech. 2015, 8(2): 177-184.DOI:10.5958/0974-360X.2015.00032.3.

14. Abdullah AG.Sedeeq BI.Azzubaidi MS. Histopathological changes in liver tissue after repeated administrations of an intermediate dose of coenzyme Q10 to Wistar Rats. Research J. Pharm. Tech. 2021; 14(8): 4025-8.DOI:10.52711/0974-360X.2021.00697.

15. Rani VU.Sudhakar M. Ramesh A. Protective effect of Puerariatuberosa Linn. in arsenic induced nephrotoxicity in rats. Asian J. Pharm. Res. 2017; 7(1): 15-20.DOI: 10.5958/2231-5691.2017.00003.X.

16. Mansoori AN.Gautam RK. and Tiwari PC. A Review on Genotoxicity. Asian J. Pharm. Res. 2014; 4(3): 162-165.https://asianjpr.com/AbstractView.aspx?PID=2014-4-3-7.

17. Banu N.Muthumary JP. Screening of aflatoxigenic property of some Aspergillusflavus isolated from sunflower seeds and its products at sunflower oil refineries. Research J. Science and Tech. 2010; 2(5): 102-107.https://rjstonline.com/AbstractView.aspx?PID=2010-2-5-4.

18. Khalil R.Yassin M.Yaseen SJ. Detection some Aflatoxins in some locally marketed Raw Peanuts. Research J. Pharm. and Tech 2021; 14(3):1431-1437.DOI: 10.5958/0974-360X.2021.00255.9.

19. Sukmanadi M. Effendi MH. The protective effect of Capsaicin (Capsicum annum L) against the induction of Aflatoxin B1 in hepatocytes: A study of liver Histopathology in mice (Musmusculus). Research J. Pharm. and Tech. 2021; 14(2):813-816.DOI: 10.5958/0974-360X.2021.00143.8.

20. Albonico M. Schutz LF. Caloni F. et al, In vitro effects of the Fusarium mycotoxins fumonisin B1 and beauvericin on bovine granulosa cell proliferation and steroid production. Toxicon, 2017; 128(3), 38–45. DOI:10.1016/j.toxicon.2017.01.019.

21. Park H. Park HS. Lim W. Song G. Ochratoxin A suppresses proliferation of Sertoli and Leydig cells in mice. Medical Mycology, 2020; 58(1), 71–82. DOI:10.1093/mmy/myz016.

22. Khoury Del. Fayjaloun S. Nassar M. et al. Updates on the effect of mycotoxins on male reproductive efficiency in mammals. Toxins, 2019; 11(9), 515–536. DOI:10.3390/toxins11090515.

23. Adedara IA. Nanjappa MK. Farombi EO. Et al. Aflatoxin B1 disrupts the androgen biosynthetic pathway in rat Leydig cells. Food and Chemical Toxicology : An International Journal Published for the British Industrial Biological Research Association, 2014; 65(3), 252–259. DOI:10.1016/J.FCT.2013.12.027.

24. Kudayer AM.Alsandaqchi ATA.Saleh FM.Alwan NA. Toxic Effect of Aflatoxin B1 on Heart, Lung, and Testis of Male Albino Rats: Histopathology Study. IOP Conf. Ser.: Mater. Sci. Eng., 2019; 571 012055. DOI:10.1088/1757-899X/571/1/012055.

25. Bilinska B. Hejmej A. Kotula-Balak M. Preparation of Testicular Samples for Histology and Immunohistochemistry. Methods in Molecular Biology (Clifton, N.J.). 2018. 1748, 17–36. DOI:10.1007/978-1-4939-7698-0_3.

26. Schefler WC. Statistics for the biological sciences. Addison- Wesley Publishing Company, London, 2nd ed., 1979. DOI:10.1002/bimj.19700120316.

27. Trebak F.Alaoui A.Alexandre D. et al. Impact of aflatoxin B1 on hypothalamic neuropeptides regulating feeding behavior. Neurotoxicology. 2015;49(7):165–73. Available from: DOI: 10.1016/j.neuro.2015.06.008.

28. Hassan AA. Rashid MA.Koratum K. Effect Of Aflatoxin B1, Zearalenone And Ochratoxin A On Some Hormones Related To Fertility In Male Rats. Life Sci J. 2010;7(3):64–72. Available from: https://xueshu.baidu.com/usercenter/paper/show?paperid=a0d5efc58bd49a910a627015888dd354

29. Castelino JM.Routledge MN. Wilson S. et al. Aflatoxin exposure is inversely associated with IGF1 and IGFBP3 levels in vitro and in Kenyan schoolchildren. MolNutr Food Res. 2015;59(3):574–81. DOI: 10.1002/mnfr.201300619.

30. Rasheed N.Alghasham A.Rasheed Z. Lactoferrin from Camelusdromedarius Inhibits Nuclear Transcription Factor-kappa B Activation, Cyclooxygenase-2 Expression and Prostaglandin E2 Production in Stimulated Human Chondrocytes. Pharmacognosy Res. 2016;8(2):135–41. DOI: 10.4103/0974-8490.175612.

31. Rasheed Z. Medicinal values of bioactive constituents of camel milk: A concise report. Int J Health Sci (Qassim). 2017;11(5):1–2. PMID: 29114185; PMCID: PMC5669503.

32. Muleta A. Hailu D. Stoecker BJ. Belachew T. Camel milk consumption is associated with less childhood stunting and underweight than bovine milk in rural pastoral districts of Somali, Ethiopia: a cross-sectional study. Journal of Nutritional Science, 2021; 10(9), 1–8. DOI: 10.1017/JNS.2021.75.

33. Supriya C.Girish BP.Sreenivasula Reddy P. Aflatoxin B1-induced reproductive toxicity in male rats: Possible mechanism of action. Int J Toxicol. 2014;33(3):155–61. DOI: 10.1177/1091581814530764.

34. Dohle GR. Smit M. Weber RFA. Androgens and male fertility. World Journal of Urology, 2003; 21(5), 341–345. DOI: 10.1007/S00345-003-0365-9.

35. Ebaid H. Abdel-Salam B. Hassan I. et al. Camel milk peptide improves wound healing in diabetic rats by orchestrating the redox status and immune response. Lipids Health Dis. 2015;14(1):132. DOI: 10.1186/s12944-015-0136-9.

36. El-Sawy HBI. Soliman MM. El-Shazly SA. Et al. Protective effects of camel milk and vitamin E against monosodium glutamate induced biochemical and testicular dysfunctions. ProgrNutr. 2018; 20(1):76-85. DOI: 10.23751/pn.v20i1.5870.

37. Owumi SE.Adedara IA.Akomolafe AP. Et al. Gallic acid enhances reproductive function by modulating oxido-inflammatory and apoptosis mediators in rats exposed to aflatoxin-B1. ExpBiol Med. 2020;245(12):1016–28. DOI: 10.1177/1535370220936206.

38. Mohamed AAR.Abdellatief SA.Khater SI. Ali H. Al-Gabri NA. Fenpropathrin induces testicular damage, apoptosis, and genomic DNA damage in adult rats: Protective role of camel milk. Ecotoxicol Environ Saf. 2019;181(10):548–58. DOI: 10.1016/j.ecoenv.2019.06.047.

39. Mekuria AN.Routledge MN. Gong YY.Sisay M. Aflatoxins as a risk factor for liver cirrhosis: A systematic review and meta-analysis. BMC PharmacolToxicol. 2020;21(1):1–8. Available from: DOI: 10.1186/s40360-020-00420-7.

40. Korish AA.Arafah MM. Camel milk ameliorates steatohepatitis, insulin resistance and lipid peroxidation in experimental non-alcoholic fatty liver disease. BMC Complement Altern Med. 2013;13:264. DOI: 10.1186/1472-6882-13-264.

41. Zuberu J.Saleh MIA.Alhassan AW. Et al. Hepatoprotective Effect of Camel Milk on Poloxamer 407 Induced HyperlipidaemicWistar Rats. Open Access Maced J Med Sci. 2017;5(7):852–8. DOI: 10.3889/oamjms.2017.158.

42. Li H. Xing L. Zhang M. Wang J.Zheng N. The Toxic Effects of Aflatoxin B1 and Aflatoxin M1 on Kidney through Regulating L-Proline and Downstream Apoptosis. Biomed Res Int. 2018;(8):9074861. DOI: 10.1155/2018/9074861.

43. Al-Asmari AK.Abbasmanthiri R. Al-Elawi AM. Et al. Effect of camel milk against renal toxicity in experimental rats. Pak J Pharm Sci. 2017;30(2):561–5. https://pubmed.ncbi.nlm.nih.gov/28650321/.

Received on 27.06.2022 Modified on 01.08.2022

Research J. Pharm. and Tech 2023; 16(3):1072-1078.

DOI: 10.52711/0974-360X.2023.00179

		Groups
Body wt. change (g) and relative wt (g/ 100 g bw)	Period	C	Cm	Af	AfCm
Body wt. change	21 day	35.65±2.331Ab	37.78±3.028Ab	- 27.11±3.142Ca	12.55±1.233 Bb
Body wt. change	42 day	78.92±3.427 Ba	99.26±3.898Aa	- 63.22±3.919Db	62.93±3.877Ca
Testes	21 day	1.208±0.019 Bb	1.485±0.034 Ab	1.021±0.018 Ca	1.214±0.017 Bb
Testes	42 day	1.584±0.028 Ba	1.790±0.020 Aa	0.890±0.014 Db	1.402±0.018 Ca
Epididymis	21 day	0.529±0.017 Bb	0.735±0.022 Ab	0.349±0.021 Ca	0.625±0.021 Bb
Epididymis	42 day	0.829±0.017 Ba	1.043±0.084 Aa	0.220±0.022 Db	0.725±0.021 Ca
Seminal vesicle	21 day	0.444±0.030 Cb	0.614±0.034 Ab	0.326±0.018 Da	0.535±0.022 Bb
Seminal vesicle	42 day	0.744±0.020 Ba	0.957±0.013 Aa	0.201±0.019 Db	0.624±0.010 Ca
Prostate	21 day	0.535±0.026 Cb	0.743±0.026 Ab	0.421±0.023 Da	0.646±0.024 Bb
Prostate	42 day	0.730±0.016 Ba	0.958±0.018 Aa	0.242±0.019 Cb	0.713±0.007 Ba