Ameliorative Effects of Gallic Acid on Cisplatin-Induced Nephrotoxicity in Rat Variations of Biochemistry, Histopathology, and Gene Expression

Abstract

Background. Cisplatin is a powerful chemotherapeutic drug mainly used in the treatment of solid tumors. Aggregation of the drug in renal proximal tubule cells causes nephrotoxicity and renal failure. Investigations showed nephrotoxicity as Cisplatin’s dose-limiting side effect. One of the Cisplatin toxicity mechanisms is generation of reactive oxygen species, which leads to oxidative stress and renal damage. The purpose of this study was evaluation of the modulating effects of Gallic acid on Cisplatin-induced variations including Caspase-3 and Clusterin expression and histopathological and biochemical parameters in adult male Wistar rats. Method. Rats were kept under standard condition of temperature, light, and humidity. The animals were divided into 4 groups: GpI: control group (received distilled water for 10 days); GpII: Gallic acid (alone) (50 mg/kg bw, once a day for 10 days); GpIII: Cisplatin (alone), single dose (6 mg/kg bw, I.P. on 5th day of study); GpIV: Gallic acid (50 mg/kg bw, once a day for 10 days) and also injected with single dose of Cisplatin (6 mg/kg bw, I.P., on 5th day of study). After 10 days, all rats were anaesthetized and plasma collected to estimate urea, creatinine, and uric acid. The right kidneys were removed for the study of gene expression and biochemical parameters. The left kidneys were used for histopathological studies. Results. The Cisplatin-induced nephrotoxicity was evident from the elevated levels of creatinine, urea, uric acid, and renal tissue MDA and also decreased levels of SOD, CAT, GPX, and GSH in renal tissue. Administration of Gallic acid significantly modulated nephrotoxicity markers, gene expression variations, and histopathological damage. Conclusion. Outcomes of the present investigation suggest that Gallic acid provides protection against CP-induced nephrotoxicity, but for application in people, further studies are needed.

The Mechanism of Kelulut Honey in Reversing Metabolic Changes in Rats Fed with High-Carbohydrate High-Fat Diet

“…Naringin has been found to suppress metabolic features and improve the number of functional β cells in rats [ 30 , 31 ]. Epigallocatechin gallate (EGCG) could inhibit 11βHSD1 activity and reduce cortisol levels [ 32 , 33 ], improve metabolic features and insulin sensitivity in animals [ 34 ], and renal histology [ 35 , 36 , 37 ]. p -coumaric acid could inhibit insulin resistance and increase adiponectin levels [ 38 , 39 ] Therefore, it is likely that phenolic compounds contained within KH contribute to the inhibition of MetS risk demonstrated in this study.…”

The Effect of Thyme Essential Oil on Liver Injuries Caused by Renal Ischemia-Reperfusion in Rats

“…However, improving liver function, restoring antioxidant levels, reducing inflammatory response, and reducing apoptosis can be useful in this case [20]. Previous studies found that antioxidants such as gallic acid, rosmarinic acid, and L-glutamine and selenium had the potential to reduce oxidative stress in the liver and kidney tissues and improve the function of these organs [21][22][23][24][25]. In our study, RIR increased the level of MDA, NO, and liver enzymes such as ALT, ALP, and AST, decreased activity of CAT and GPX, and decreased the level of GSH in liver tissue.…”

Cisplatin-Induced Kidney Toxicity: Potential Roles of Major NAD+-Dependent Enzymes and Plant-Derived Natural Products

“…As mentioned above, the major site of cisplatin accumulation in the nephron is the proximal tubules [ 24 , 25 , 26 ]. The entry of cisplatin into the tubular epithelial cells is thought to be mediated by two receptors: Crt1 and OCT2 (copper transporter 1 and organic cation transporter 2) [ 17 ].…”