Healing Effect of Partial Pure Lignan against Renal Impaired Induced by High Fat Diet

 

Zahraa Ahmed Okhti, Baydaa H. Abdullah, Mayssaa E. Abdalah

Clinical Laboratory Science Department, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq.

 

ABSTRACT:

Background: Hyperlipidemia is a routine way that may lead to damage effects on renal architecture. Hence, this work aimed to assesses both hyperlipidemia and the healing impact of lignan on histological of the kidney. Methods: Rabbits were divided into four groups, as the following: first Group ـ diet free cholesterol for one month, second Group - diet with 1600mg/kg cholesterol for one month, third Group - diet with 1600mg/kg cholesterol for one month then received orally 40mg/kg/day of partial pure of SDG for two weeks. Removed kidney quickly to histological analysis. Results: Marked atrophy of glomeruli with dilated Boman space and large vacuolated of fatty changes of renal tubules, fibrosis and hyaline cast in the lumen of renal tubules beside that, in another section were seen thrombus in dilated blood vessels when animal suffer from hyperlipidemia. on another side, disappeared of atrophy, fibrosis, and thrombus when treated with partial pure lignan. Conclusions: These findings show that partial pure lignan leads to improving renal structure in rabbits models of hyperlipidemia.

 

 

 

1. INTRODUCTION:

Currently, Obesity is the most common disease, and it is a high association with a different disease such as renal disorder which is a significant problem, and its pathophysiological are not fully understood¹. For instance, Hyperlipidemia, and hypertension, alter renal action, but in a various way².  Kidneys alterations appear to be a sequel to obesity; also, growth factors and hormones are well known, have a complex etiology³.

 

Proof from previous studies supposed that malnutrition can lead to many diseases like liver failure, hypertension, and kidney diseases⁴. Dietary inequality in fat models animal leads to abdominal obesity⁵.

 

Fatty liver disease⁶, and splenomegaly⁷ has been cleared previously. Besides, used to quantify renal morphology^8,9. De Castro et al. showed that a fat diet in young rats induces higher increased visceral lipid stores, constituting the best nutritional interventions to induce metabolic syndrome in rats¹⁰, for that supposed The kidney might be an important link in our understanding of the interactions between abnormalities in lipid metabolism and vascular disease. There is now abundant evidence demonstrating that the kidney is a major target, and it is possible that lipid-induced renal alterations. Thus, sufficient renal damage caused by abnormalities in lipid metabolism could result in additional deleterious effects on circulating lipoproteins. Histological studies have also pointed to a strong relationship between systemic atherosclerosis and renal damage.

 

In the present research, we try to detect a high-fat diet (HFD) effects on histological features of the male rabbit's ҆ kidney and positive role of lignin (SDG) to amelioration renal injury.

 

 

2. MATERIALS AND METHODS:

2.1  Extraction of the compound:

Linum usitatissimum was powdered by blender; the powder was extracted continuously by the soxhlet apparatus first with petroleum ether and secondly with chloroform. Finally completed all steps of extraction, according to Okhti et al.¹¹.

 

2.2 Preparation of Partial Pure compound:

This step was done by taking (40mg/ml) of partial pure lignan and dissolving (0.04g) with Distell water, depending on previous reports¹².

 

2.3 Animals:

In our present research, 20 male pathogens Free, wild type rabbits were used.  The mean rabbits' weight was 1600mg. All rabbits were purchased from Iraq, then divide into four groups. Each group has a specific system in its diet according to previous work¹¹.

 

2.4 Histopathological Examination:

All groups of animals were sacrificed, the heart was removed quickly and fixed in (10%) formaldehyde solution, dehydrated in alcohol and impregnated in wax. Cutting at four μm, slides were stained with routine stain, then examined under compound light microscopic for diagnosis any alteration of architectural ҆s tissues according to steps of previous work¹³.

 

3. RESULT:

Microscopic findings of renal sections from HFD- rabbits are outlined as follows. Kidney histopathological section of animals administrated with cholesterol revealed marked atrophy of glomerular tuffs with dilated bowman space and large vacuoles of fatty changes in epithelial lining cells of renal tubules Fig(1), also, marked fibrosis around glomeruli and replacement of renal tubules which contain hyaline cast in their lumen Fig (2); In other slides, it was reported thrombus in dilated blood vessels that expressed hypertrophy of muscular layer Fig (3). Numerous inflammatory cells and blood vessels congested between renal tubules which expressed vacuolar degeneration in their epithelial lining cells were recorded Fig (4), on another side, observed histopathological section of kidney of animal administrated with cholesterol and treatment with partial pure SDG shows only mononuclear cells aggregation around blood vessels and between renal tubules Fig(5).

 

 

Figure )1  (Histopathological section  in the kidney of animal administration with cholesterol shows  marked atrophy of glomerular tuffs with dilated  Boman  space            and large  vacuoles of fatty changes in epithelial lining cells of renal tubules               (H&E stain 40X)

 

Figure) 2(: Histopathological section  in the kidney of animal administration with cholesterol shows marked fibrosis around  glomeruli                and replacement of renal tubules which contain  hyaline cast in their lumen            (H&E stain 40X)

 

 

Figure (3): Histopathological section  in the kidney of animal administration with cholesterol shows  thrombus                in dilated blood vessels that expressed hypertrophy of the muscular layer                 (H&E stain 40X).            

 

Figure (4): Histopathological section  in the kidney of animal administration with cholesterol shows numerous  inflammatory cells and blood vessels congested                which exhibit vacuolar degeneration of  their epithelial lining  cells              (H&E stain 40X)

 

Figure (5): Histopathological section  in the kidney of animal administration with cholesterol and treatment with SDGshows  mononuclear cells aggregation around  blood vessels  and  between renal tubules                (H&E stain 40X)

 

4. DISCUSSION:

(HFD) induced increased mean total cholesterol, reduced HDL cholesterol, induced liver disease, and renal inflammation; our finding appeared that HFD rabbits male is the best diet interventions to induce lipid metabolisms disorder. Other reports improved hyperlipidemia induces renal damage in a different animal model such as dietary provoke hyperlipidemia in rabbit¹⁴.

 

Our histological examination showed marked fibrosis around glomeruli and hyaline cast in the lumen of renal tubules which are seen in figure (2), and agree with Vázquez- Pérez et al., that confirmed a hypocholesteremia correlate with increase in size of kidney and damage of glomeruli, and refer to high levels of plasma cholesterol in rabbits causes renal capillary damage and vascular functional change¹⁵.

Several studies^16-18. have shown that renal disorders, such as vasodilatation, glomerular hyper filtration and inflammation, are results of obesity progressed. De Castro2 et al. showed that Young animals – high-fat diet showed renal inflammation, along with central obesity¹⁰. furthermore, detected glomerular atrophy and fibrosis are seen in figures (1 and 2) which supported by others reports¹⁹. Also, these changes may be an association with an increase in the mesangial matrix, cellularity and an increase in epithelial cells of tubular. Also, it was observed alteration in tubular such as fatty degeneration and proliferation of epithelial cells. From previous works supposed different mechanisms can be changed in renal architecture, the first mechanism cleared hyperlipidemia may be induced renal damage by acting on renal cells. Renal Tubular and glomerulus represent the best site for lipid accumulation because structure of glomerular and tubular capillaries which be fenestrated and absence of a basement membrane between the mesangium, therefore, Lipids easily pass these sites. Low-density lipoprotein (LDL) cholesterol bind to Mesangial cells²⁰, as well as, play a vital role in the pathogenesis of kidney. A second mechanism that can induce chronic renal inflammation involves high infiltrating macrophages by induced high expression of chemo-attractants toward glomerulus^21,22 and into the tubulointerstitium^23-25, of affected animals, this mechanism is proved by Pesek-Diamond et al.²⁵, that lowering macrophages leads to a reduction of renal damage and glomerulosclerosis. The confirmed steps at the deleterious role of hyperlipidemia on the kidney is still undetermined. On other hand, current analysis demonstrated that use partial pure of SDG as supplement reduced glomerular inflammatory, disappeared fibrosis and lesion of tubule interstitial in rabbits models of hypercholesterolemia, that agreement with  Hall et al.¹⁷,  that clearing a renal protective role of flax seed in mouse infected with chronic inflammation of kidney²⁶. Flax seed is a richest plant of lignans for that reason chooses it as a source for SDG²⁷. In addition, Lignans have anti-proliferative roles^28,29, which also may be reduced proliferation of renal epithelial cells and renal pathy²⁶. Furthermore, SDG has antioxidant activity^30-32.  Otherwise, other study proposed that SDG has a renal moderated effect in a mouse infected by lupus nephritis.  

 

Finally, deduce there is a reflective relationship between fat feed and structural alteration of the kidney such a tubular injury prominent dilatation of the renal vessels and tubules, glomerular fibrosis and atrophy, but, when uses partial pure SDG as anti-lipemic agents, will observed moderates of renal pathy by reduced tubule-interstitial and glomerular injury. Therefore recommended treatment hypercholesterolemia with SDG as a supplement may best preserve the way of renal function.

 

5. ACKNOWLEDGMENTS:

The authors thanks Mustansiriyah University for its expert to helpful assistance to done this work and special thanks to Pharmacy College/Mustansiriyah University for its supported to completed this work.

 

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Accepted on 17.04.2020           © RJPT All right reserved

Research J. Pharm. and Tech 2021; 14(3):1251-1254.