Amelioration of Cisplatin and Gentamicin Induced Kidney Damage by Caryota urens and Hyophorbe lagenicaulis

 

Das Saumya*, Mazumder Avijit, Gautam Anamaika, Nashra, Hrithik Gupta

Noida Institute of Engineering and Technology, Pharmacy Institute, Knowledge Park-II,

Greater Noida, Uttar Pradesh, 201306.

*Corresponding Author E-mail: awasthi.saumya22@gmail.com

 

ABSTRACT:

Background: Nutraceutical potentiality of the plants on the basis of their efficacy and huge phytochemicals present in the aerial parts of Caryota urens(flowers) and Hyophorbe lagenicaulis(leaves) were taken as the background of the study. Aim: The present study investigated the nutraceutical activity and nephroprotective potentiality of Caryota urens flowers and Hyophorbe lagenicaulis leaves against cisplatin and gentamycin induced nephrotoxicity were performed. Materials and Methods: The extract of Caryota urens flowers and Hyophorbe lagenicaulis leaves were screened for preliminary phytochemical analysis,in vitro antioxidant activity andin vivo acute toxicity test was also performed by following OECD guideline 420. In vivo screening for cisplatin and gentamycin induced nephrotoxicity preclinically were also done. Result: It was found that CUFE and HLLE (1:1) suspension administered orally to the albino Wistar rats, no major side effects were seen in any of the experimental animal. The findings obtained from the experimental data were showed that the effect of CUFE and HLLE as potent nutraceuticals in cisplatin and gentamycin induced nephrotoxicity was significant (**p<0.001). Conclusion: These findings concluded that the CUFE and HLLE (1:1) have potent bioactive phyto-pharmaceuticals and natural source of antioxidants present with them. Both the plants have nutritionally rich source of dietary food supplements and due to this they are also helpful in successfully managing commercial drugs induced nephrotoxicity.

 

KEYWORDS: Nutraceuticals, Phytochemical, Cisplatin, Gentamycin, Nephrotoxicity.

 

 


INTRODUCTION: 

Nutraceuticals are dietary components naturally found in foods and believed to have a health benefit, including protecting and treating from many chronic diseases. Nutraceutical provides a better immune system.1 For health care benefits completely understands the mechanism of action of major nutraceuticals food supplements and their possible efficacy in anti-aging and to improve RBC level, VLDL level, and with other health care benefits.2 Discoveries gave us prompts to continue for useful food advancement having nutraceutical potential.3

 

The possible mechanisms of their activity, evidence for potential health promoting activity, antioxidants and these phytochemicals in nutrition as substitutes for synthetic antibiotic activity promoters has also been addressed.4,5 Caryota urens(family: Arecaceae) is widely known as the fish tail palm. The palm tree as a whole is native to Sri Lanka, India, Myanmar, and Malaysia, where it fills up fields and jungle clearings. 6 It is said to have originated in Cambodia. Urens is Latin for "stinging," and refers to the compounds found in Caryota urens fruit. Solitary fishtail palm, kitul palm, toddy palm, wine palm, sago palm, and jaggery palm are some of the common names in English.7,8  The promising cancer prevention by Caryota urensand α-glucosidase restraint these herbal extractsare supposed to most likely because of the presence of bioactive phyto-pharmaceuticals present in them which acts as a potent nutraceutical elements.9,10 Hyophorbe lagenicaulis (family Arecaceae) commonly known asbottle palm or palmiste gargoulette, is a species of flowering plant. It is native to Round Island, Mauritius.11,12 Inspite of effective role of Caryota urens and Hyophorbe lagenicaulis in folk traditional medicines, till date not appropriate scientific evidences are available on their biological activities and phytochemical distribution. 13,14 Both the selected plants are nutritionally rich therapeutic values and contains a combination of flavonoids, carotenoids, phenolics, phytoestrogenes and saturated fatty acids and sugars like sucrose, glucose, and fructose, andfurther new sap has shown potential for refreshments.15,16 Micronutrients are one of the major groups of nutrients our body needs. It contains essential minerals, biotin, fibers rich elements, macronutrients, prebiotic nutrients, and antioxidant vitamins or other essential elements that improve our health conditions.5 It may be consumed as a dietary supplement or as a functional food unit which is a derivative of many isolated herbal plants with many medicinal properties.17 These nutraceutical-based products play an essential role in human health.18 The majority of the peoples are consuming all these herbal based nutraceutical products, which has safety and therapeutic effects. In the recent study of certain areas, such as raw material has uniformity and find the ability of good source of dietary and have the potential effect of these nutraceuticals.19

 

However, detailed analysis of health promoting bioactive compounds and antioxidants are present, especially in Himalayan wild edible flowers or leaves. The research on encompasses the main sources of these chemicals present in the herbal plant Caryota urens L flowers and Hyophorbe lagenicaulis leaves.20, 21Bioactive compounds and antioxidant potential of the richest source of total phenolics; for flavonoids; for ascorbic acid and for beta-carotene. Phenolic compounds, i.e. gallic acid varied among species. 22Antioxidant activity showed the significant relation with total phenolics, flavonoids and phenolic compounds. 23, 24 Keeping in mind all this background the current research work was aimed to perform the in-vitro antioxidant and in-vivo nephroprotective activity of Caryota urens and Hyophorbe lagenicaulis by cisplatin and gentamycin induced nephrotoxicity using experimental animal model.

 

 

a) Caryota urens palm tree,

 

b) Caryota urens flowers (Fishtail palm)

 

c) Hyophorbe lagenicaulis palm tree

 

d) Hyophorbe lagenicaulis leaves

Fig.1.

 

MATERIAL AND METHODS:

Collection and Authentication:

The flowers of Caryota urens and leaves of Hyophorbe lagenicaulis were collected from NIET (Pharmacy Institute), Knowledge Park-II, Greater Noida in November 2019. It was authenticated by Dr. Anjula Pandey (Taxonomist), National Bureau Plant Genetic Resources (NBPGR), Pusa grounds, New Delhi. A voucher (specimen no: NHCP/NBPGR/2020-23) is protected in the herbarium segment by the ordered branch of NBPGR, New Delhi.

 

Extraction of plant materials:

The aerial parts of both plant materials of Caryota urens and Hyophorbe lagenicaulis were shaded dried. Each one of the dried powdered samples was extracted with ethanol solvents upto 96 hours. The dried flower and leaf (150g) of Caryota urens and Hyophorbe lagenicaulis were extracted independently with ethanol (500ml) using the soxhlet apparatus. The liquid extracts were concentrated by using hot water bath set at 60˚C then kept in a hot water bath to get more solid extract. The dry extract was then stored at 4°C until used.

Phytochemical analysis of the aerial part of Caryota urens flowers extract and Hyophorbe lagenicaulis leaves extract:

A wide range of phytochemical components present in the extract of Caryota urens flowers and Hyophorbe lagenicaulis leaves. They were screened by preliminary phytochemical screening methods.25,26

 

In vitro Antioxidant Activity Study:

Antioxidantactivity of both the extracts,Caryota urens flowers (CUFE) and Hyophorbe lagenicaulis leaves (HLLE) were determined by following the two methods- DPPH free radical scavenging activity and hydrogen peroxide free radical scavenging activity.27,28

 

DPPH free radical scavenging activity:

Estimation of the free radical scavenging activity of CUFE and HLLE (1:1) ratio was done by DPPH free radical scavenging activity. The absorbance of ethanol preparation of 2,2-diphenyl1-1-picryl-hydroxyl (DPPH) was carried by UV spectrophotometer.

% inhibition = Absorbance of the control - Absorbance of the test/Absorbance of Control x 100.

 

Hydrogen peroxide scavenging activity:

The free radical scavenging activity of CUFE and HLLE in the hydrogen peroxide (H₂O₂) model was also identified. The arrangement of H₂O₂ (40mm) was set up in phosphate buffer pH 7.4 and the concentrated solution was identified by observing the abs at 560nm using a UV spectrophotometer.

% scavenged hydrogen peroxide = 1- Absorbance (standard)/Absorbance (control) x100.

 

In vivo Pharmacological Studies:

Oral acute toxicity study of CUFE and HLLE (1:1)according to OECD guidelines 420

Group I: Test drug (CUFE and HLLE) 5mg/kg, was suspended in 1% CMC w/v, P.O

 

Group II: Test drug (CUFE and HLLE) 50mg/kg, was suspended in 1% CMC w/v, P.O

Group III: Test drug (CUFE and HLLE) 300mg/kg, was suspended in 1% CMC w/v, P.O

Group IV: Test drug (CUFE and HLLE) 2000mg/kg, was suspended in 1% CMC w/v, P.O

 

Albino Wistar rats were separated into 4 groups (Group I, Group II, Group III, and IV) of n=6 animals of both sex (3 Males and 3 Females) each. Test medication of CUFE and HLLE (1:1) at different given doses of 5mg/kg, 50mg/kg, 300mg/kg, 2000 mg/kg body weight was suspended in carboxymethyl cellulose (CMC) and administration orally in the wistar rats.

 

Cisplatin induced nephrotoxicity:

In cisplatin induced nephrotoxicity, induction of kidney damage was done by experimentally induced single dose of cisplatin. The animal groups of Albino Wistar rats were divided into 3 groups. Group 1- Negative control group, Group 2- Standard Group of α-tocopherol (150mg/kg) (I.P), Group 3 Received extract of (CUFE and HLLE) (1:1)with single-dose 100mg/kgsuspended in 1% CMC w/v and administeredoralroute + Cisplatin (20mg/kg)IVroute. After administration of the test drug CUFE and HLLE (1:1) suspension, animals were observed daily upto 21 days. Any toxic signs in the experimental animals were observed carefully. Then the animals were sacrificed as per the guidelines and kidney further sent for the histopathological findings. 29,30

 

Gentamycin induced nephrotoxicity:

In the gentamycin induced nephrotoxicity, the Albino Wistar rats were separated into 3 groups (n-6). Group 1- Negative control group, Group 2- Standard Group- α-tocopherol 150mg/kg (I.P route), Group 3- Received extract of (CUFE and HLLE) (1:1)with single-dose 100mg/kgsuspended in 1% carboxymethyl cellulose (CMC) w/v and administeredoralroute + Gentamycin (80mg/kg)I.P route. After administration of the test drug CUFE and HLLE (1:1) suspension, animals were observed daily for upto 21 days. Any toxic signs in the animals were observed. Then the animals were sacrificed and observed for any major nephrotoxicity signs. 31,32

 

Histopathological Study:

At the end of the 21st day, food was withheld from the Albino Wistar rats, and they were fasted overnight but the animals had easy access to water. Under strong ether anaesthesia, the animals were killed and slaughtered through cervical dislocation. Surgically, the kidney was removed. After, following that, the isolated kidneys were immersed in 10% formalin for 1 hour (diluted to 10% with normal wine) to avoid shrinking of the organ utilized for histological investigations.Blood free kidney was taken out and stored in the containers separately filled with formalin (10% v/v). It was incubated at 37oC under aseptic conditions for histopathological evaluation under the microscope.33,34

 

RESULTS AND DISCUSSION:

Phytochemical analysis of the aerial part of Caryota urens flowers extract(CUFE) and Hyophorbe lagenicaulis leaves extract (HLLE):

The plants Caryota urens and Hyophorbe lagenicaulis havelarge variety of phyto-constituent's presentsuch as alkaloids, flavonoids, phenols, oxalic acid, organic compounds and inorganic mixtures, etc. Distinctive essential metabolites were found with high concentration in their extracts. The presence of terpenoids, oxalic acid, phenols and flavonoidsin CUFE and HLLE have shown strong antioxidants       properties.24, 35 Terpenoids have antioxidants as well as anti-cancer properties and promote the plant growth regulators by glutathione s-transferase. Oxalic acid also have antioxidants properties, they act as primary chelator of calcium.It is used as a nutraceutical for health benefits with healthy weight gains property. Protein was present in less concentration in CUFE as compared to HLLE. 20

 

In vitro Study of Antioxidant Activity:

DPPH free radical scavenging activity

Table: 1. Antioxidant activity of standard drugα-Tocopherol (Vitamin E) as % inhibition of DPPH free radical scavenging

S. No.

Drug Concentration (µg/ml)

α-Tocopherol (Absorbance) 295nm % inhibition

1.

10 µg/ml

0.039 nm

2.

20 µg/ml

0.044 nm

3.

40 µg/ml

0.052 nm

4.

60 µg/ml

0.064 nm

5.

80 µg/ml

0.073 nm

Theeffect of antioxidant activity ofstandard drug α-tocopherol (Vitamin-E) was showed the % inhibition of DPPH free radical scavenging activity at different concentrations.

 

Table: 2. Effect of CUFE and HLLE (1:1) in DPPH free radical scavenging activity

S. No.

Extract

Concentration (µg/ml)

Inhibition %

1.

CUFE and HLLE (1:1)

10µg/ml

13.15±1.010

2.

CUFE and HLLE (1:1)

20µg/ml

21.16±1.714

3.

CUFE and HLLE (1:1)

40 µg/ml

41.37±1.589*

4.

α-tocopherol

40µg/ml

52.72±1.926*

Values were estimated as mean ± SD of each group. The effect of CUFE and HLLE (1:1) showed the % inhibition of free radical scavenging activity was found to be 41.37%* as compared to the reference standard drug α-tocopherol 52.72%*. The p-value was found to be*p<0.01 for bothCUFE and HLLE.

 

Fig.2. Effect of standard drug α- tocopherol by DPPH free radical scavenging methodfree radical scavenging method

 

Fig.3. Effect of standard drug α-Tocopherol by percentage inhibition of DPPH

 

In In vitro antioxidant activity, free radical scavenging activity of CUFE and HLLE (1:1) ratio was performed by DPPH free radical scavenging method. The absorbance of ethanol preparation of 2, 2-diphenyl1-1-picryl-hydroxyl (DPPH) was carried by UV spectrophotometer. 17The DPPH free radical scavenging activity was estimated by α-tocopherol as standard drug. Variousconcentration of the CUFE and HLLE (1:1) with α-tocopherolwas prepared to check thefree radical scavenging activitywith the initial concentration 40 µg/ml. Absorbance was estimated at 295nm after 30 mins by using a UV spectrophotometer. The % inhibition of free radicals was calculated with reference standard. As depicted in figures 3 and 4, the free radical scavenging abilityof CUFE and HLLE (1:1)was shown. The results were tabulated in Table:2.

 

Theeffect of anti-oxidantwere showedas % inhibition of DPPH free radical activity at different concentrations of test and standard drugs.The % inhibition of free radical scavenging activity was increased as the concentration of CUFE and HLLE (1:1) rises, at 40µg/ml concentration the % inhibition was found to be 41.37% as compared to the standard drugα-tocopherol which was 52.72%.

 

Hydrogen peroxide scavenging activity:

Table: 3. Effect of CUFE and HLLE(1:1) in hydrogen peroxide scavenging method

S. No.

Drug Concentration (µg/ml)

CUFE and HLLE (1:1) (%)

α-Tocopherol (%)

1.

0.0625

15.79±0.008

11.11±0.016

2.

0.125

33.35±0.012

15.61±0.007

3.

0.25

41.62±0.007

19.25±0.005

4.

0.5

59.68±0.019*

27.41±0.004*

5.

1

64.72±0.03**

38.12±0.02**

Values were estimated as mean ± SD of each group. The effect of CUFE and  HLLE (1:1) showed good scavenging activity compared with the reference standard drug α-tocopherol. At 0.5µg/ml of the % inhibition was found to be 59.68 and 27.41% respectively. At 1µg/ml of the % inhibition was found to be 64.72 and 38.12 % respectively. The p-value was found to be *p<0.01 and **p<0.001 for both standard and test drugs.

 

Fig.4. Effect of CUFE and HLLE (1:1) in % inhibition of free radical scavenging activity by DPPH methodscavenging activity by Hydrogen peroxide method

 

Fig.5. Effect of CUFE and HLLE (1:1) in % inhibition of free radical

 

The antioxidant effect of CUFE and HLLE (1:1) was also evaluated by using Hydrogen peroxide scavenging method. Sample were prepared in ethanol solvent at5 different concentrations (0.0625, 0.125, 0.25, 0.5 and 1µg/ml) of CUFE and HLLE (1:1) and reference standard drug α-tocopherol respectively. The absorbance was detectedfor both test and standard drug by UV spectrophotometerat 295nm. The % inhibition of test drug and the reference standard was calculated.The effect of CUFE and HLLE (1:1) showed good H2O2scavenging activity compared with the reference standard drug α-tocopherol. At 0.5µg/ml of the % inhibition was found to be 59.68 and 27.41% respectively and at a dose of 1µg/ml of the % inhibition was found to be 64.72 and 38.12 % respectively. The p-values was found to be *p<0.01 and **p<0.001 for both standard and test drugs.

 

Statistical Analysis:

It was estimated that the CUFE and HLLE (1:1) suspension contains a considerable amount of antioxidant compounds with high anti-oxidative value and free radical scavenging activities and all experimental measurements were calculated as a normal of three examinations ± SD. The investigations were determined by the student t-test and p-values were calculated by single direction ANOVA. The*p<0.01 and **p<0.001 were viewed as critical point.

 

In vivo Pharmacological Studies:

Determination of oral acute toxicity:

Table: 4. Oral acute toxicity test (according to OECD guidelines 420)

S. No

Group no.

0 Day (g)

1 Day (g)

2 Day (g)

Total Body weight (g)

1

Group I- CUFE and HLLE (1:1) Suspended

5mg/kg

160.73 ± 3.57

163.91 ± 2.13

172.97 ± 2.90

25.14 ± 1.15 NS

2

Group II- CUFE and HLLE (1:1) Suspended

50mg/kg

164.47 ± 4.10

171.38 ± 5.16*

189.70 ± 5.94*

25.96 ± 2.76*

3

Group III- CUFE and HLLE (1:1) Suspended 300mg/kg

170.37 ± 5.10

181.46 ± 6.36**

195.70 ± 6.94**

26.59 ± 4.26**

4

Group IV- CUFE and HLLE (1:1) Suspended 2000mg/kg

175.47 ± 5.70

189.97 ± 6.59***

194.47 ± 7.61***

27.09 ± 5.39***

CUFE (Caryota urens flowers extract) and HLLE (Hyophorbe lagenicaulis leaves extract). The mean values were estimated mean as ± SEM of 6 rats in each group.The p-value was found to be *p<0.05, **p<0.01 and *** p<0.001, NS: non-significant at different concentrations of test drugs.

 

Fig. 6. Effect of CUFE and HLLE (1:1) suspension (100 mg/kg) in rats at various days (on day 0, day 1, and day 2)

 

To study the oral acute toxicity of CUFE and HLLE (1:1) suspensionby using OECD 420 guideline, no any major adverse reaction or mortality in experimental animalwas observed. The dose levels of CUFE and HLLE (1:1) suspensionwere 5 mg/kg, 50 mg/kg, 300 mg/kg, and 2000 mg/kg during the entire period of experimentation. There were no clinical signs of toxicity or abnormal behaviours on any of the treated experimental animals were observed.

 

Cisplatin Induced Nephrotoxicity Model:

Test of hematological parameters of cisplatin induced nephrotoxicity

Table: 5. Effect of blood profile in cisplatin induced nephrotoxicity

S. No.

Hematological parameters nephrotoxicity

Group I

[Negative control +cisplatin]

Group II

[CUFE and HLLE (1:1) suspension +cisplatin]

Group II

[α-tocopherol +cisplatin]

1

HB (g/dl)

11.14 ± 1.41

13.55 ± 1.62**

12.96 ± 1.65*

2

RBC (m/mm3)

7.92 ± 0.34

8.52 ± 0.34**

8.12 ± 0.56*

3

WBC(m/mm3)

8.21 ± 1.08

9.33 ± 0.62*

9.13 ± 0.90**

5

MCH(pg)

15.35 ± 1.55

15.43 ± 1.67**

16.35 ± 1.81*

6

MCHC %

31.28 ± 1.82

33.38 ± 1.62**

30.88 ± 1.22*

7

Total Cholesterol (mg/dl)

95.14 ± 5.81

97.27 ± 4.91**

105.27 ± 4.61*

8

TG (mg/dl)

92.07 ± 11.60

95.07 ± 11.60**

103 ± 1.87*

9

Glucose(mg/dl)

97.85 ± 5.95

98.19 ± 4.85**

106.15 ± 5.55*

10

Creatinine(mg/dl)

0.52 ± 0.06

0.53 ± 0.05**

0.55 ± 1.03*

11

Urea (mg/dl)

36.78 ± 1.49

33.98 ± 1.58**

38.83 ± 1.77*

The effect of CUFE and HLLE (1:1) suspension was compared with that of the control group and the standard group treated animals. All the values were expressed in the mean ±SEM of six rats in each group. For a given portion, Non-significant (NS) and significant value presented at *p<0.01 and **p<0.001.

 

 

Fig.7. Effect of CUFE and HLLE (1:1) on on hematological compared with negative control and standar

 

 

Fig. 8. Effect of CUFE and HLLE (1:1) on hematologicalparametersofparameters of Hb RCB and WBC compared with negative control and standar

 

Fig. 9. Effect of CUFE and HLLE (1:1) on hematological parameters of total cholesterol level of VLDL, TG, BGL, Cr and Urea compared with negative control and standard

 

The effect of various hematological parameters in cisplatin induced nephrotoxicity was estimated in experimental rats at the end of 21 days of drug treatment.36Estimation of Hb, RBC, WBC, MCHC, MCH, and MCH levels were increased, the blood glucose level was normalized and there was a decrease in Cr, BUN and VLDL levels were observed in CUFE and HLLE treated rats as shown in Table: 5.

 

The findings of hematological parameters showed that the test drugs CUFE and HLLE (1:1)are responsible for the better health                 effects as compared to the control group. Reduction in the serum of Cr, BUN, and total cholesterol level or VLDL level in                 cisplatin-treated rats were also showed to improve the health conditions of the treated rats so, thetest drugs CUFE and HLLE (1:1) are considered as the potent herbal nutraceutical as they improve the haematological profile as well as acts as a nephroprotective agent in the treated animals group.

 

 


 

Gentamycin Induced Nephrotoxicity Model:

Test of hematological parameters of gentamycin induced nephrotoxicity:

Table: 6. Effect of blood profile of gentamycin induced nephrotoxicity study

S. No.

Hematological parameters

Group I

[Negative control + gentamycin]

Group II

[CUFE and HLLE (1:1) suspension+ gentamycin]

Group II

[α-tocopherol+ gentamycin]

1

HB (g/dl)

10.14 ± 1.71

12.45 ± 1.65*

13.76 ± 1.36**

2

RBC (m/mm3)

6.92 ± 0.34

7.82 ± 0.34**

7.22 ± 0.86*

3

WBC(m/mm3)

7.21 ± 1.08

8.09 ± 0.89*

8.83 ± 0.20**

5

MCH(pg)

14.15 ± 1.50

15.43 ± 1.57*

16.35 ± 1.71**

6

MCHC %

31.82 ± 1.28

32.84 ± 1.26*

33.18 ± 1.82**

7

Total Cholesterol (mg/dl)

96.54 ± 5.56

99.77 ± 6.91**

103.49 ± 4.61*

8

TG (mg/dl)

93.07 ± 11.10

98.01 ± 10.60**

108.22 ± 1.88*

9

Glucose(mg/dl)

96.85 ± 4.95

99.19 ± 4.85**

105.55 ± 5.55*

10

Creatinine (mg/dl)

0.64 ± 0.06

0.51 ± 0.05**

0.59 ± 1.01*

11

Urea (mg/dl)

36.74 ± 1.49

37.79 ± 1.28**

38.83 ± 1.27*

 


The effect of CUFE and HLLE (1:1) suspension was compared with that of the control group and the standard group treated animals. All the values were expressed in mean ±SEM of six rats in each group. For a given portion, Non-significant (NS) and significant at value presented at *p<0.01 and **p< 0.001.

 

Fig. 10. Effect of CUFE and HLLE (1:1) on hematological parameters

 

 

Fig. 11. Effect of CUFE and HLLE (1:1) on hematological parameters of Hb compared with negative control and standard of RCB and WBC compared with negative control and standard

 

 

Fig. 12. Effect of CUFE and HLLE (1:1) hematological parameters of total cholesterol

 

VLDL, TG, BGL, Cr and Urea compared with negative control and standard

 

The effect of various hematological parameters in gentamycin induced nephrotoxicity was estimated in experimental rats at the end of 21 days of drug treatment. Estimation of Hb, RBC, WBC, MCHC, MCH were done.37MCH levels were increased as compared to control groups, the blood glucose level was normalized and there was a significant decrease in Cr, BUN and VLDL (total cholesterol level) were observed in CUFE and HLLE treated rats as shown in the Table: 6.

 

Histopathological Study:

Cisplatin induced nephrotoxicity

 

(A)

 

(B)

 

(C)

Fig. 13. Histopathology of kidney: (A) Negative control with Cisplatin, B) CUFE and HLLE with Cisplatin and C) α-Tocopherol with Cisplatin

 

Histopathological studies of organ (kidney) was performed and concerned images were depicted in figure no. 13.After the 21 days of the treatment time frame, the histopathological observations from the experimental rat’s kidney, sections showed (A) Microscopic section of kidney of negative control rats showed sporadic cells and stromal cell damage. In glomeruli, mesangial cellularity was increased. In tubules, a residue of destroyed cells, a single layer, and cuboidal cells appeared and focal lymphoplasmacytic infiltrate was observed. (B) Nephrotoxicity induced animal treated with CUFE and HLLE (1:1) with single-dose 100mg/kg suspended in 1% (CMC) + Cisplatin (20mg/kg) showed prominent recovery in glomeruli architecture and significantly decreased in the infiltration of lymphocytes, plasma cells in the stroma, and glomeruli.(C) Nephrotoxicity induced animal treated with α-tocopherol (150mg/kg)+Cisplatin (20mg/kg) showed prominent recovery as same in test group from cisplatin-induced changes in the smallest cells of the kidney (nephron). It indicated α-tocopherol was able to restore normal histological architecture of kidney.

 

Gentamycin induced nephrotoxicity:

 

(A)

 

(B)

 

(C)

Fig. 14: Histopathology of kidney: (A) Negative control with Gentamycin, B) CUFE and HLLE with Gentamycin and C) α-Tocopherol with Gentamycin

 

After 21 days of the treatment time frame, the histopathological observations from the experimental rats kidney, were showed (A) Microscopic section of kidney negative control rats showed that the single layer renal sporadic cells and cell disarrangements. In glomeruli, mesangial cellularity was increased. In tubules, in a residue of destroyed cells, a single layer, cuboidal cells appeared and focal lymphoplasmacytic infiltrate was observed. (B) Nephrotoxicity induced animal treated with CUFE and HLLE (1:1) 100mg/kg suspended in 1% (CMC) + gentamycin (80mg/kg) showed prominent recovery in glomeruli architecture and significantly decreased the infiltration of lymphocytes, plasma cells in the stroma and glomeruli. It also a mild increase in mesangial cellularity.(C) Nephrotoxicity induced animal treated with α-tocopherol (150mg/kg) + gentamycin (80mg/kg) showed prominent significance with gentle assurance from initiated changes in the stroma cells of the kidney (nephrons). It indicated α-tocopherol was able to restore normal histological architecture of kidney.

 

The intensity of cisplatin and gentamycin induced nephrotoxicity essentially causes tubules interstitial injuries and decreases body weight were recorded. Cisplatin causes toxicity in the renal tubules, mainly in the fragment of the external medulla and mitochondrial expansion in the kidney nephrons. The reports of the intensity of cisplatin and gentamycin induced pathological damage in the kidney and its prevention by CUFE and HLLE (1:1) suspension was observed. In both cisplatin and gentamycin induced nephrotoxicity models, the CUFE and HLLE (1:1) suspension was significantly effective. CUFE and HLLE (1:1) was found to be more potent in cisplatin induced nephrotoxicity after 21 days of test drug administration as compared to the gentamycin induced nephrotoxicity. This protective effect is might be due to the presence of rich amount of antioxidants present in both the plants which works synergistically when given in combination.38,39 Based on the above findings, it was concluded that the impact of CUFE and HLLE against cisplatin and gentamycin induced nephrotoxicity in Wistar rats was observed to be beneficial. Thus CUFE and HLLE are acting as potent nutraceutical by preventing vital organ damage (kidney) due to the commercially available synthetic drugslike cisplatin and gentamycin. Hence nutraceuticals along with the potent antioxidant property can be beneficial for preventing synthetic drug induced nephrotoxicity.40-42

 

CONCLUSION:

Caryota urens and Hyophorbe lagenicaulis both plants are considered multipurpose and have various therapeutic efficacies in all the vital organs (multiorgan). Present investigation has clearly showed that the Caryota urens flowers extract and Hyophorbe lagenicaulis leaves extract (CUFE and HLLE) (1:1) suspension have great bioactive components and a nutritionally rich source of food suppliment. It was the first time that the extract obtained from the aerial parts of Caryota urens and Hyophorbe lagenicaulis administered orally in the suspension form for the evaluation of nutraceutical supplementation that showed potent antioxidant and prevention from cisplatin and gentamycin induced nephrotoxicity in experimental animals.So both of the plants can be considered as a good nutraceutical for the management nephrotoxicity seen inthe commercially available drugs.

 

ACKNOWLEDGMENT:

The authors are thankful to the college management of the NIET, Pharmacy Institute 19-Knowledge Park II, Institutional Area, Greater Noida, UP, India for providing support, encouragement, and motivation to carry out the work.

 

CONFLICT OF INTEREST:

The author has no area of conflict interest.

 

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Received on 17.12.2021             Modified on 27.07.2022

Accepted on 31.12.2022           © RJPT All right reserved

Research J. Pharm. and Tech 2023; 16(3):1274-1282.

DOI: 10.52711/0974-360X.2023.00210