Comparative biochemical and histopathological studies on the efficacy of metformin and Nigella sativa oil against thioacetamide-induced acute hepatorenal damage in rats

Abstract

Background: Metformin is the first-line oral anti-diabetic drug and Nigella sativa (NS) have been used as traditional medicine to cure/prevent a wide range of diseases in different part of the world, particularly in Saudi Arabia. Objective: To carry out the comparative biochemical and histopathological studies on the efficacy of metformin, Nigella sativa oil (NSO) against thioacetamide (TAA)-induced acute hepatorenal damage in rats. Materials and methods: Forty-eight male Albino Wistar rats were randomly divided in to eight groups with six rats in each group. Group-I (normal control): received normal saline (1 ml/kg, p.o.), group II (toxic control): received normal saline (1 ml/kg, p.o.) and TAA (500 mg/kg, i.p.), group-III (NSO per se): NSO (2 ml/kg, p.o.), group IV (metformin per se): metformin (250 mg/kg/d, p.o.), group V (NSO+TAA): NSO (2 ml/kg/d p.o.)+TAA (500 mg/kg, i.p.): group VI (metformin+TAA): metformin (250 mg/kg/d, p.o.) +TAA (500 mg/kg, i.p.). Group VII (NSO+metformin +TAA): NSO (2 ml/kg, p.o.), and metformin (250 mg/kg/d, p.o.)+TAA (500 mg/kg, i.p.), group VIII (TAA+Jigreen): jigreen (1 ml/kg/d, p.o.)+TAA (500 mg/kg, i.p.). Normal saline, NSO, metformin and jigreen were administered to respective groups by gastric intubation for 7 consecutive days. On the 7 th d, 1 h after the drugs treatment, a single intraperitoneal injection of TAA (500 mg/kg,) was administered to the rats of all groups except groups I, III and IV to induce acute liver and kidney injury. All animals were sacrificed under ether anesthesia after 24 h of TAA administration. The liver and kidney function tests in the serum were evaluated to assess the toxic effects of TAA as well as the protective effects of the given treatments against TAA induced the hepatorenal toxicity. Histopathology of liver and kidney tissues was also carried out to validate the findings of biochemical investigation. Results: The results indicated that the TAA intoxicated rats showed significant increase in the alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), lipid profile, uric acid, urea, creatinine, while no significant changes were observed in serum levels of calcium, magnesium and phosphorus as compared with normal control rats. In the treatment groups, combination drug therapy showed remarkable alleviation of hepatorenal toxicity in metformin plus NSO group and was congruent to that of the standard polyherbal preparation "jigreen". The histopathological studies also support the hepatorenal protective effects of metformin and NSO. Conclusion: The results of the study demonstrated that metformin+NSO protects liver and kidney against acute TAA toxicity. Overall, this study proved the ameliorative effects of metformin, NSO and metformin plus NSO combination against TAA induced hepatorenal toxicity in rats.

Metformin Ameliorates Oxidative Stress Induced by Diabetes Mellitus and Hepatocellular Carcinoma in Rats

“…Since Met is positively charged, it enters into the mitochondria of hepatocytes and inhibits ATP production, which in turn, results in the acute inhibition of gluconeogenesis. Also, it was previously reported that Met suppresses liver inflammation by inhibiting interleukin-6-stimulated inflammatory response via activation of AMP-activated protein kinase (AMPK) (44). Moreover, Met may promote the stabilization of phospholipid in the cell membrane thereby preserving cell integrity, and ultimately prevents the cellular escape of cytoplasmic components and enzymes from the hepatocytes into the bloodstream.…”

Catharanthus roseus Combined with Ursolic Acid Attenuates Streptozotocin-Induced Diabetes through Insulin Secretion and Glycogen Storage

“…The obtained serum was then held back at lower temperature (2-3°C) for further measurement of different biochemical study. Serum insulin and glucose levels were determined by enzymatic methods with the help of an automated analyzer (Dimension Vista® system, Siemens, Germany) using standard biochemical kits [19]. 2.8.…”

Pharmacological studies on the efficacy of a thymoquinone‐containing novel polyherbal formulation against cisplatin‐induced hepatorenal toxicity in rats

“…It has been reported in many studies that cisplatin, when administered, can be retained in the body for as long as 20 years. It has a protective effect on different kinds of tissues like the heart, kidney (Ahmad & Alkreathy, 2018;Hassan, Akhtar, Ahmed, Ahmad, & Najmi, 2017;Nagi, Al-Shabanah, Hafez, & Sayed-Ahmed, 2011), skin, and liver (Jaswal, Sinha, Bhadauria, Shrivastava, & Shukla, 2013). Endogenous antioxidants in therapeutic herbs may assume a critical part as a defense against oxidative damage and ensure the biological functions of cells (Gaikwad, Dagle, Choughule, Joshi, & Kadam, 2012).…”

“…Thymoquinone (TQ), a flavonoid derived from Nigella sativa seeds, generally known as black cumin, is diversely used in traditional medicinal systems to treat various ailments (Ahmad et al, , 2014. It has a protective effect on different kinds of tissues like the heart, kidney (Ahmad & Alkreathy, 2018;Hassan, Akhtar, Ahmed, Ahmad, & Najmi, 2017;Nagi, Al-Shabanah, Hafez, & Sayed-Ahmed, 2011), skin, and liver (Jaswal, Sinha, Bhadauria, Shrivastava, & Shukla, 2013). Recent findings have concluded that TQ has an ameliorative effect against oxidative stress and inflammatory responses (Mahmoud, Ahmed, & Galaly, 2014).…”