Vanillic acid ameliorates docetaxel-induced hepatotoxicity in rats via modulation of TLR4/MyD88/TRAF6, NF-κB, and JAK/STAT signaling pathways.

Docetaxel (DTX) is an efficient and normally used anticancer drug. But it results in systemic organ toxicity and damages various non-target organs of the body. Vanillic acid (VA) is a biologically active phenolic acid that exhibits potential therapeutic properties. This research was conducted to understand the protective effects of VA against DTX-induced liver damage in rats. Forty male Sprague Dawley rats were randomly assorted into four groups. One group was the control, and the other groups were as follows: DTX group, DTX + VA group, and VA group. Thirty milligrams per kilogram DTX was given once on the first day of the trial while VA (50 mg/kg) was given on a daily basis via intragastric gavage for 7 days. The results showed that DTX disrupted TLR4/MyD88/TRAF6, NF-κB, and JAK/STAT signaling pathways and caused oxidative stress, inflammation, and apoptosis as well as mitochondrial and histological damages in liver. However, the supplementation of VA protected the hepatic tissues from these damages by mitigating the effects of DTX. VA protected the hepatic tissues by reducing the expressions of TLR4, MyD88, TRAF6, NF-κB, and other inflammatory cytokines, while upregulating the expressions of IκB. Importantly, it lowered the levels of ALT and AST by 29.10% and 44.46%, respectively, while significantly reducing the levels of inflammatory markers, i.e., TNF-α (36.60%) and IL-6 (40.94%). Additionally, ELISA evaluation showed it lowered the levels of p-STAT3, and NF-κB (p-65) and normalized BAX, BCL-2 and CASPASE-3 expressions and levels. Furthermore, VA restored antioxidant defenses and preserved mitochondrial and histological architecture. Hence, VA may protect hepatic tissues from chemotherapeutic drug, i.e., DTX-induced damage through modulating JAK/STAT, and NF-κB/TLR4 signaling pathways.