Dexpanthenol Attenuates High-Fructose Corn Syrup-Induced Hepatic Injury in Young Adult Rats by Modulating Oxidative Stress, Apoptosis, and Inflammasome-Associated Pyroptotic Signaling

Abstract

Excessive intake of high-fructose corn syrup (HFCS) contributes to pediatric metabolic dysfunction-associated steatotic liver disease, but the mechanisms linking fructose exposure to inflammatory cell death remain incompletely defined. This study investigated whether dexpanthenol (DEX) attenuates HFCS-induced liver injury by modulating oxidative stress, apoptosis, and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome-associated pyroptotic signaling. Thirty-two young adult male Wistar rats were assigned to control, HFCS, HFCS+DEX, and DEX groups (n = 8 each). HFCS-induced liver injury was established with 20% HFCS-55 in drinking water for 8 weeks. DEX (500 mg/kg/day, intraperitoneally) was administered from the end of week 4 to week 8. Liver tissues were assessed by histopathology; immunohistochemistry for caspase-3, malondialdehyde, and proliferating cell nuclear antigen; biochemical measurement of total antioxidant and oxidant status; and RT-qPCR analysis of Nlrp3, caspase-1, gasdermin D, and interleukin-1β. HFCS exposure caused steatosis, inflammation, and necrosis; increased histopathological scores; enhanced caspase-3, malondialdehyde, and proliferating cell nuclear antigen expression; elevated total oxidant status; and markedly upregulated inflammasome-related genes. Total antioxidant status did not differ among groups. DEX significantly improved hepatic architecture; reduced immunohistochemical markers of oxidative stress, apoptosis, and injury-associated proliferation; and downregulated NLRP3, caspase-1, gasdermin D, and interleukin-1β expression. These findings suggest that DEX attenuates HFCS-induced liver injury through a multi-target mechanism involving suppression of oxidative damage, apoptosis, and inflammasome-associated pyroptotic signaling in young adult rats.