Ameliorative effects ofN‐acetyl cysteine on diclofenac‐induced renal injury in male rats based on serum biochemical parameters, oxidative biomarkers, and histopathological study

Abstract

Diclofenac (DIC) can cause nephrotoxicity in humans. In this study, we evaluated the protective effects of N‐acetyl cysteine (NAC) on DIC‐induced nephrotoxicity. Rats were assigned to four groups. Group 1 was control group; group 2 administrated with DIC only; group 3 administrated with DIC plus NAC and group 4 was treated with DIC and silymarin. Then, the oxidative biomarkers in serum and kidney were evaluated. In group 2, DIC caused a remarkable elevation (p < 0.05) in the levels of serum uric acid, TNF‐α, creatinine, urea, GOT, and GPT, protein carbonyl, malondialdehyde (MDA), and renal TNF‐α gene expression, relative to control group. In treated groups with NAC and silymarin, a noticeable reduction (p < 0.05) was seen in mentioned levels of biochemical parameters. NAC showed that it could reduce the abnormality of biochemical parameters and histopathological changes which is induced by DIC. Practical applications N‐acetyl cysteine (NAC) has a potential to ameliorate renal histopathological changes and improving renal activity of antioxidant enzymes in nephrotoxicity by diclofenac. Also, NAC has a potential to reduce inflammatory gene expression in the diclofenac‐induced nephrotoxicity. Additionally, NAC can be considered as an antioxidant which reduces renal MDA and serum protein carbonyl due to nephrotoxicity by diclofenac.

Carvacrol exerts nephroprotective effect in rat model of diclofenac-induced renal injury through regulation of oxidative stress and suppression of inflammatory response

“…Additionally, the inordinate creation of free radicals as a result of DIC administration was associated with the elevated protein-oxidation reaction, which in turn lead to the augmentation of PC contents, indicating that protein oxidation could be one of the mechanisms that participated in DIC-induced renal injury. These observations are in accordance with earlier researches [ 34 , 46 ]. In this study, the administration of CAR decreased DIC-mediated oxidative stress in the renal tissue by reducing the amount of PC.…”

“…The amount of Malondialdehyde (MDA) is an indicator of lipid peroxidation (LPO), which shows the activation of oxidative stress within the cells [ 41 ]. In this study, the amount of MDA was considerably augmented in the DIC-treated rats, which was in accordance with the results of the earlier researches [ 34 , 38 ]. Furthermore, treatment with CAR after exposure to DIC not only caused a rise in FRAP level but also caused a decline in MDA content in the renal tissues and sera.…”

“…The considerable elevation in the amount of creatinine, urea, and uric acid after exposure of rats to DIC may be a sign of kidney impairment. These findings suggested that probably DIC leads to a reduction in GFR of the animals, which in turn caused the elevation in the serum levels of some biochemical marker [ 34 , 35 , 36 ]. On the other hand, when CAR could diminish the serum levels of Cr, urea, and uric acid in rats after exposure to DIC, it could be assumed that probably this agent might have an ameliorative effect on DIC-induced nephrotoxicity through increasing GFR.…”

“…We also reported a considerable augmentation in GPT and GOT contents, two important biochemical markers indicating hepatocellular and renal damages [ 34 ], in those rats which were exposed to the single-agent of DIC. This finding was in agreement with the results reported previously [ 37 , 38 ].…”

Gallic acid mitigates diclofenac-induced liver toxicity by modulating oxidative stress and suppressingIL-1βgene expression in male rats

“…In addition, the excessive production of ROS following DIC exposure was related to the high levels of protein oxidation reaction, leading to the formation of protein carbonyl (PC) levels, signifying that oxidative protein damage might be one of the mechanisms of DIC induced liver toxicity. These observations are in line with previous investigations (Nouri and Heidarian 2019 ; Nouri et al. 2017 ).…”