Comparative protective effect of N‐acetyl cysteine and tetramethylpyrazine in rats with gentamicin nephrotoxicity

Abstract

Gentamicin (GM) is used against serious and life‐threatening infections, but its use is limited by the occurrence of nephrotoxicity, which involves the generation of free radicals. In this work we tested the effect of a compound with antioxidant properties, tertamethylpyrazine (TMP), on GM‐induced nephrotoxicity, and compared it with an established anti‐oxidant compound N‐acetyl cysteine (NAC). Six groups of rats were studied: (1) control, treated orally (p.o.) and intraperitoneally (i.p.) with saline; (2) treated i.p. with GM (80 mg kg‐1 per day for 6 days); (3) TMP, given p.o. (100 mg kg‐1 per day for 10 days) + GM (same dose as above during the last 6 days); (4) NAC, given i.p. (500 mg kg‐1 per day for 10 days) + GM as above; (5) TMP (100 mg kg‐1 per day for 10 days) + saline; (6) NAC (500 mg kg‐1 per day for 10 days) + saline. GM nephrotoxicity was characterized by reduced creatinine clearance, increased creatinine and urea concentrations in plasma. These functional and structural alterations were prevented or ameliorated by NAC treatment, while TMP had only a slight mitigating effect. The concentration of GM in the renal cortex of the rats given GM + NAC (but not TMP) was lower than that found in rats treated with GM alone. The mechanism by which NAC and, to a lesser extent TMP, protected against GM‐induced nephrotoxicity may be related, at least in part, to the decrease in oxidative stress in renal cortex.

Several Alkaloids in Chinese Herbal Medicine Exert Protection in Acute Kidney Injury: Focus on Mechanism and Target Analysis

“…This explains the strong antioxidant capacity of these alkaloids by regulating the endogenous Nrf2/HO-1 system, while the decrease of Keap1 allows more Nrf2 to be free, thus providing more kidney protection [15,74]. In vitro experiments, pre-treatment of NAC (10 mM) and TMP (50, 100 mM) also fully blocked the upregulation of HO-1 protein induced by As induced HK-2 cells, and inhibited ROS production [64]. In addition, TMP, other mechanisms involved in AKI, such as inflammation [63] and apoptosis [75], were also significantly improved.…”

“…), reduces KIM-1 levels in rat models of AKI [43]. It has been reported that TMP can increase the level of GSH, SOD, and CAT induced by ROS production in renal cells induced by As or CP [43,63,64]. Oxidative stress is also the main molecular mechanism of I/R-AKI.…”