Thymoquinone mitigates diclofenac-induced hepatorenal toxicity in male Wistar rats by balancing the redox state and modulating Bax/Bcl-2/caspase-3 apoptotic pathways and NF-κB signaling

Amir Safi , Shakila Mohammadi, Mina Emami, Alireza Radaei, Ali Kalantari-Hesari, Ali Nouri, Mohammad Rahimi-Madiseh , Reza Ahmadi

Abstract


Background and purpose: Diclofenac (DF), a widely used non-steroidal anti-inflammatory drug, can induce hepatotoxicity and nephrotoxicity. This study investigated the protective effects of thymoquinone (TQ), a bioactive compound from Nigella sativa, against DF-induced organ damage in rats.

Experimental approach: Forty-eight male rats were divided into six groups (8 each) and treated orally for seven days as follows: group 1 (control): normal saline; group 2: DF (50 mg/kg); group 3: DF (50 mg/kg) + silymarin (50 mg/kg); groups 4-6: DF (50 mg/kg) + TQ at 10, 20, or 40 mg/kg, respectively. Serum biochemical parameters, hepatorenal oxidative stress markers, pro-inflammatory cytokines, and apoptosis-related genes were assessed. Histopathological examinations of liver and kidney tissues were also performed.

Findings/Results: DF administration induced significant liver and kidney damage, evidenced by elevated serum biochemical markers, increased oxidative stress, inflammation, apoptosis-related gene expression, and histopathological alterations. TQ treatment, particularly at the highest dose (40 mg/kg) effectively attenuated these changes. TQ improved liver and kidney function, reduced oxidative stress markers, suppressed inflammation, modulated apoptosis-related gene expression, and ameliorated histopathological damage.

Conclusion and implication: TQ exerted significant protective effects against DF-induced hepatorenal toxicity in rats, potentially through its antioxidant, anti-inflammatory, and anti-apoptotic properties. These findings suggest that TQ may be a promising therapeutic agent for mitigating DF-induced organ damage. However, further research, including clinical trials, is needed to confirm its efficacy and safety in humans.

 

 


Keywords


Apoptosis; Diclofenac; Hepatorenal toxicity; Inflammation; Oxidative stress; Thymoquinone.

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