Paracetamol-Induced Renal Tubular Injury

Abstract

Abstract. Paracetamol (also known as acetaminophen) causes acute and chronic renal failure.

Vitamin E (α tocopherol) attenuates toxicity and oxidative stress induced by aflatoxin in rats

“…58,59 Several studies have reported that the intoxication of AFB 1 causes nephrotoxicity. 60 Administration of AF caused a significantly higher concentration of plasma creatinine and urea. This result is compatible with results of Rati et al 61 The heightened appearance of plasma creatinine of AFB 1 -treated rats indicates the increased transformation of phosphocreaine to creatinine in the muscle, which might be due to utilization of phosphocreatine in muscular contraction.…”

Mechanisms of Renal Apoptosis in Health and Disease

“…67 Similar observations were made with acetaminophen. 68 This suggests some changes in apoptosis-related molecules are epiphenomena not directly related to cell death. By contrast, Bax-mediated mitochondrial injury and caspase activation are key events in CsA-induced apoptosis of tubular cells.…”

“…79,81 Acetaminophen upregulates CHOP/ GADD153, leading to caspase-12 cleavage and apoptosis in tubular cells. 68 Caspase inhibition by BcxL protects tubular cells from acetaminophen-induced apoptosis but not from eventual cell death. 82 In this regard, BclxL interacts with ER proteins such as BAP31, RTN-XS, NSP-C, and the BH3-only protein Spike.…”

“…76 Acetaminophen induces caspase-dependant apoptosis of tubular cells without characteristic mitochondrial alterations or involvement of Bax. 68 Acetaminophen nephrotoxicity is an example of involvement of the ER in apoptosis. ER-initiated apoptosis is triggered by disturbances in calcium homeostasis or accumulation of misfolded proteins and multiple signaling pathways emerging to promote cell death through caspase-dependent and independent means, including the recruitment of the mitochondrial pathway ( Figure 4B).…”

Endoplasmic reticulum stress as a novel target to ameliorate epithelial-to-mesenchymal transition and apoptosis of human peritoneal mesothelial cells

“…26,52 Cytoprotection by ER stress preconditioning was also confirmed in cultured renal tubular cells exposed to nephrotoxic drugs via the induction of GRP78 and an enhancement of ER folding capacity. [53][54][55] In this study, preconditioning targeting ER stress ameliorated TGF-β1-induced EMT and apoptosis in HPMCs, suggesting the role of ER as a potential target for protecting the peritoneal membrane. ER stress preconditioning in HPMCs may enhance the maturation of protein by enhancing GRP expression, which resulted in the preservation of peritoneal membrane integrity.…”