Protective effect of malvidin against fipronil-induced oxidative stress, inflammation and apoptosis in mice

The aim of this study was to investigate the protective activity of malvidine against fipronilinduced oxidative stress, inflammation and apoptosis in mice. A total of 48 CD-1 male mice were used in the study. A total of 4 groups (n:12) were formed as control, FPN, MLV and MLV+ FPN groups. The control group received 0.9% NaCl (5 mg/kg c.a) containing 0.1% dimethylsulfoxide (DMSO) by gavage for 14 days. FPN group received FPN by gavage at 5 mg/kg/b.w./day for 14 days and MLV group received malvidin hydrochloride by gavage at 5 mg/kg/ b.w./day (in 0.9% NaCl) for 14 days. In the group in which MLV+ FPN was given together, malvidin hydrochloride (5 mg/kg/b.w/day by gavage) was given 2 hours before fipronil (5 mg/kg/b.w/day by gavage) for 14 days. The study was terminated on day 15 and blood, liver, kidney and brain samples were collected from the mice. Serum samples were analyzed for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzyme activities, creatinine and blood urea nitrogen (BUN) levels. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-α) activities and glutathione (GSH) levels were analyzed in liver, kidney and brain homogenates, malondialdehyde (MDA), nuclear factor kappa B2 (NF-κB2), nuclear transcription factor erythroid-2-like factor 2 (Nrf2), interleukin-1β (IL-1β) and 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. Histopathologic and immunohistochemical examinations were also performed in liver, kidney and brain samples. There was a significant increase (p<0.05) in serum AST, ALT, creatinine and BUN values in the group given fipronil compared to the control group, and a significant decrease (p<0.05) in serum AST, ALT, creatinine and BUN values in the group given malvidin+fipronil together compared to the group given fipronil alone. In liver, kidney and brain tissue homogenates, there was a significant increase in MDA, NF-κB, 8-OHdG, TNF-α and IL-1β levels, iNOS and COX-2 activities in the fipronil-administered group compared to the control group; a significant decrease (p<0.05) was detected in the activity of SOD, CAT and GPx enzymes and in GSH and Nrf2 levels. In the group in which group given malvidin+fipronil was administered together, there was a significant decrease (p<0.05) in MDA, NF-κB, 8-OHdG, TNF-α and IL-1β levels, iNOS and COX-2 activities compared to the group where fipronil was given alone; a significant increase (p<0.05) was determined in the activity of SOD, CAT and GPx enzymes and in GSH and Nrf2 levels. In addition, in the fipronil treated group, a significant increase (p<0.001) in caspase-3, caspase-9 and Bax expressions and a significant decrease (p<0.001) in Bcl-2 expressions were detected in the histopathological changes in both liver, kidney and brain tissues of the animals compared to the control group. In the group given malvidin+fipronil together was administered together, there was a significant decrease in pathological lesions in the tissues, a significant decrease in caspase-3, caspase-9 and Bax expressions (p<0.001) and a significant increase in Bcl-2 expressions (p<0.001). Based on these findings, it was determined that fipronil administered at a dose of 5 mg/kg c.a caused liver, kidney and brain damage, while malvidin administration prevented its toxicity on liver, kidney and brain by reducing oxidative stress, inflammation, apoptosis, tissue damage markers and histopathological changes. In conclusion, it was concluded that malvidin can be used as an antioxidant, anti-inflammatory and antiapoptic protective agent against fipronil induced liver, kidney and brain damage.