Role of Oxidative Stress in Drug-Induced Kidney Injury

Abstract

The kidney plays a primary role in maintaining homeostasis and detoxification of numerous hydrophilic xenobiotics as well as endogenous compounds. Because the kidney is exposed to a larger proportion and higher concentration of drugs and toxins than other organs through the secretion of ionic drugs by tubular organic ion transporters across the luminal membranes of renal tubular epithelial cells, and through the reabsorption of filtered toxins into the lumen of the tubule, these cells are at greater risk for injury. In fact, drug-induced kidney injury is a serious problem in clinical practice and accounts for roughly 20% of cases of acute kidney injury (AKI) among hospitalized patients. Therefore, its early detection is becoming more important. Usually, drug-induced AKI consists of two patterns of renal injury: acute tubular necrosis (ATN) and acute interstitial nephritis (AIN). Whereas AIN develops from medications that incite an allergic reaction, ATN develops from direct toxicity on tubular epithelial cells. Among several cellular mechanisms underlying ATN, oxidative stress plays an important role in progression to ATN by activation of inflammatory response via proinflammatory cytokine release and inflammatory cell accumulation in tissues. This review provides an overview of drugs associated with AKI, the role of oxidative stress in drug-induced AKI, and a biomarker for drug-induced AKI focusing on oxidative stress.

Cytochrome P450-2E1 is involved in aging-related kidney damage in mice through increased nitroxidative stress

“…The aged kidneys undergo many significant changes during the aging process such as inflammation, glomerulonephropathy, glomerulosclerosis, cell apoptosis, and renal fibrosis which indirectly reflects kidney aging (Hodgin et al, 2015; Martin and Sheaff, 2007; Percy et al, 2008). Interestingly, and in agreement with the “free radical theory of aging” (Harman, 1956), oxidative stress along with oxidative protein modifications have been correlated with kidney toxicities, acute and chronic kidney diseases, and aged kidney with deteriorating functions (Hodgin et al, 2015; Hosohata, 2016; Martin and Sheaff, 2007; Pedraza-Chaverri et al, 2016; Percy et al, 2005; Percy et al, 2008; Poulianiti et al, 2016; Small et al, 2012). …”

Efficacy of curcumin on prevention of drug‐induced nephrotoxicity: A review of animal studies

“…Successful identification of the markers of oxidative stress is critical to the understanding and managing DIN. Primary markers of oxidative stress include lipid peroxidation (LPO), glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) …”

“…Primary markers of oxidative stress include lipid peroxidation (LPO), glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). 45,77,[80][81][82] Various study designs and animal models have been used to evaluate the efficacy of potential treatments for DIN. Antunes et al explored the effectiveness of prophylactic curcumin and selenium treatment for protection against renal injury and LPO induced by cisplatin in Wistar rats.…”

Levofloxacin-ceftazidime administration regimens combat Pseudomonas aeruginosa in the hollow-fiber infection model simulating abnormal renal function in critically ill patients

“…Doses of antibacterial therapy need to be adjusted for ICUs patients. This is because the kidney is the main organ for drug elimination, so without dose adjustment, the accumulation of drugs and their metabolites in plasma would increase the possibility of toxicity [2]. At present, the resistance to P. aeruginosa is increasing [3].…”