Effect of Cellgevity®, a Glutathione-Enhancer Dietary Supplement, on Streptozotocin-Induced Type-2 Diabetes and Nephrotoxicity in Rat

Abstract

Background: Diabetic nephropathy (DN), a diabetes-induced nerve damaging effect on the kidney structure and function due to hyperglycaemia is a major microvascular complication. Hyperglycaemia causes uremia, hypercreatininemia, declined glomerular filtration rate, and decreased levels of serum protein and albumin. This condition leads to progressive decline in renal function resulting in renal insufficiency and End-Stage Renal Disease. The prevalence of DN in Africa has increased significantly in recent years, emphasising the importance of developing new preventive and treatment therapies. Despite the fact that there are different medications used to manage DN, most of these drugs are associated with serious unwanted side effects that contributes to the many complications observed in DN patients. This has paved way for the search for newer and better therapeutic agents that can better manage the disease and, at the same time, causing very less side effects. It was hypothesised that Cellgevity® could provide protection from diabetes and its complications. Aim: To evaluate the hypoglycaemic and nephroprotective potentials of Cellgevity® in healthy and type-2 diabetic nephropathy rat models. Methods: Seventy (70) male Sprague-Dawley rats with an average weight of 200 g were grouped into10 groups of seven rats each (n = 7). All rats were subjected to an overnight fast for 12 hours after which type-2 diabetes mellitus (T2DM) was induced using streptozotocin (STZ) (60 mg/kg b.wt) and nicotinamide (NA) (110 mg/kg b.wt). After 24-hours of STZ-NA injection, rats with fasting blood glucose (FBG) greater than 11.1 mmol/L were considered diabetic and divided into 8 groups. Group 1 of the diabetic rats received distilled water (diabetic negative control). Groups 2, 3, and 4 were orally administered with varying doses of Cellgevity® (40 mg/kg b.wt; 80 mg/kg b.wt; 160 mg/kg b.wt respectively); Group 5 and 6 received 15 mg/kg b.wt and 20 mg/kg b.wt of glibenclamide (Glib) and captopril (Cap) respectively. Group 7 and 8 of the diabetic rats received combinations of either Cellgevity® and Glib or Glib and Cap. Two additional groups (non-diabetic rats) served as normal controls. Blood samples were taken by tail snip and FBG were measured at specific days (1, 3, 6, 9, 12, 15, 22 and 29) following induction of T2DM. At the end of the experiment (29th day), the animals were sacrificed, and their blood, kidneys and pancreas harvested for haematological, biochemical, and histological studies. Results: Diabetic rats showed a significant increase in FBG (30.33 mmol/L, p<0.001), serum creatinine (81.20%) and urea (110%) with a corresponding decrease in total protein (47.94%) and albumin (75.46%) when compared to the normal control rats. The Cellgevity® doses, 40 mg/kg b.wt and 80 mg/kg b.wt significantly decreased (p<0.001) FBG from 30.33 to 17.33±3.69 mmol/L and 17.35±9.07 mmol/L respectively. The Glib dose (15 mg/kg b.wt) reduced levels of FBG from 30.33 to 9.85±3.96 mmol/L within the 28-day treatment period. Also, there was a significant increase (p<0.01) in serum albumin (ALB, 176.52%), total proteins (T.PROT, 79.13%) and white blood cell count (WBC, 154.98%) in diabetic rats administered with Cellgevity® when compared to the diabetic control rats. Serum ALB levels in diabetic rats administered with single therapy of Glib and combined form (Glib plus Cap) increased significantly (p<0.01) by 109.30% and 210.83% respectively in comparison with the diabetic control rats. Furthermore, Glib and Glib plus Cap markedly increased T.PROT by 27.10% and 61.87% respectively when compared to the diabetic control. Administration of Cellgevity® (low dose) resulted in 68.78% and 55.87% decrease in serum CREA and urea respectively. Similarly, the groups that were administered with Glib and Glib plus Cap had a decrease in serum CREA by 56.61% and 58.69% respectively in comparison with diabetic control rats. Kidney histological sections (40X) showed noticeable alterations (shrank glomeruli tuft, ballooned bowman space) in the diabetic control rat in comparison with the diabetic positive control rats. Conclusion: The study demonstrated that administration of Cellgevity® (40, 80 mg/kg b.wt) reduces FBG level and protects against nephrotoxicity in STZ-NA induced type-2 diabetic rats. This study could justify the use of Cellgevity® in the management of nephropathy in diabetic patients. Further study (clinical trial) should be conducted in humans to confirm this finding.