The Consequence of Antioxidant Signaling Pathways on Acetaminophen Nephrotoxicity

Renal injuries and death from renal diseases are one of major issues in medical field nowadays. Proper right dose of over-the-counter oral analgesic medication is important to be more controlled and decrease health risk. Acetaminophen is a commonly used over the counter oral analgesic and antipyretic, and it should be used at the appropriate therapeutic dose. Herein we shed the light on the potential impact of thymoquinone, turmeric and -lipoic acid (either alone or in several combinations) on AP-induced renal injury and to explore the underlying mechanisms and signaling pathways of antioxidants under investigation. N-acetyl cysteine was used as a reference antidote drug. Acute AP on nephrotoxicity was elucidated in male Wister rats 24hr after the administration of an overdose of oral AP (1000 mg/kg). The investigated antioxidants were administered 3hr before that and carried on for 72hr after AP intoxication. The administration of AP enhanced the secretion of renal biomarkers including serum urea, creatinine, and uric acid. As well as the production of inflammatory biomarkers including C-reactive protein, toll like receptor-4, nuclear factor kappa-B (NF- B) and ameliorated apoptotic biomarker P53. On the other hand, renal tissue showed a marked depletion in glutathione level in addition to the elevation of nitric oxide and malondialdehyde amount. Overexpression of fibrotic biomarkers, including transforming growth factor (TGF- 1) was detected. However, P53 was downregulated compared to the corresponding level in the control group. In conclusion, treatment with the antioxidants altered inflammatory and apoptotic biomarkers. Importantly, the combination regimen of LA and turmeric showed the most reno-protective impact via the upward of anti-inflammatory and antioxidant signaling.