Protocatechuic acid through modulation of signaling pathways and oxidative stress exerts protective effects in rat model of carbon tetrachloride-induced renal and reproductive toxicities

Protocatechuic acid (PCA) exhibits a broad spectrum of pharmacological activities including antioxidative action and modulation of signaling pathways. This study examines modulatory effect of PCA against carbon tetrachloride (CCl 4 )-induced toxicities on the kidney and testes of rats. Rats were treated as follows: group 1 (olive oil), group 2 was given CCl 4 only intraperitoneally at 3 ml/kg in a suspension of olive oil, groups 3 and 4 were pretreated with PCA orally at 10 and 20 mg/kg respectively for 7 days before CCl 4 challenge. Biochemical investigations were carried out by assessing serum biochemical markers, testicular hormones levels and sperm parameters, oxidative stress markers, expression levels of NF-kB, COX2 and TNF, antioxidant enzymes activities, and histopathological changes. Data revealed that PCA reduced the elevated level of urea by CCl 4 ( P < 0.05), ameliorated induced oxidative stress, and restored antioxidant enzymes’ activities in both organs. Also, an improvement in sperm quality and hormonal profile of rats treated with PCA when compared with CCl 4 -treated rats was observed. Furthermore, PCA inhibited the activation of NF-kB, COX2, and TNF in rats. Histopathological reports confirmed the biochemical findings. The results demonstrated that PCA strengthens the antioxidant defense mechanism against CCl 4 -induced renal and testicular toxicity via modulation of signaling pathways and oxidative stress.