Proanthocyanidin protects against cisplatin-induced oxidative liver damage through inhibition of inflammation and NF-κβ/TLR-4 pathway

Abstract

Although cisplatin (CIS) is a highly effective anticancer drug, hepatotoxicity is one of the most common adverse effects associated with its use. Recently, reactive oxygen species (ROS) and inflammation are suggested to be key factors in the pathophysiology of CIS-induced acute liver damage. The aim of this study is to investigate the possible protective effect of proanthocyanidin (PRO) against CIS-induced acute hepatotoxicity. Rats were divided into four groups: 1, Control; 2, PRO; 3, CIS; and 4, PRO + CIS. Biochemical studies and histopathology were used to assess liver damage. ROS, inflammatory cytokines, nuclear factor kappa beta (NF-κβ), inducible cyclooxygenase enzyme (COX-2), inducible nitric oxide synthase (iNOS), toll-like receptor-4 (TLR-4) gene expression, and apoptotic markers were also assessed. PRO pretreatment protected the liver against CIS-induced toxicity as indicated by decreased plasma levels of liver function enzymes and the normal liver histopathology observed in the PRO + CIS group. PRO pretreatment also diminished indicators of oxidative stress in the liver, including nitric oxide (NO) and malondialdehyde (MDA). It also increased the antioxidants, reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) in the liver. Plasma interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) were all reduced. Liver gene expression of NF-κβ, COX-2, iNOS, and TLR-4 were all downregulated. Furthermore, PRO administration downregulated the liver expression of the apoptotic marker, Bax, while upregulated the antiapoptotic marker, Bcl2. In conclusion, our results revealed that PRO may protect against CIS-induced acute liver damage mainly through inhibition of ROS, inflammation, and apoptosis.

Protective Effect of Sika Deer (Cervus nippon) Velvet Antler Extract against Cisplatin-Induced Kidney and Liver Injury in a Prostate Cancer PC-3 Cell Xenograft Model

“…Our results appeared to be consistent with many previous findings that indicated the nephrotoxic and hepatotoxic effect of Cis, its association with increased free radical formation, and the subsequent induction of oxidative and nitrosative stress [17,[50][51][52]. Inflammation plays an important role in the initiation and progression of Cis-induced kidney and liver damage [53][54][55][56]. Cis induces the release of a series of proinflammatory cytokines (TNF-α, IL-1β, COX2, and iNOS) and causes the infiltration of leukocytes and macrophages into damaged renal tissues [57].…”

PTEN promotes apoptosis of H2O2‑injured rat nasal epithelial cells through PI3K/Akt and other pathways

“…Meanwhile, H 2 O 2 treatment reduced SOD and CAT levels, especially in PTEN overexpressing cells while additionally increasing MDA levels compared with control cells. SOD and CAT are essential natural scavengers of superoxide radicals and hydrogen peroxide to prevent organisms from undergoing oxidative stress injury (36). MDA, the final product of lipid oxidation, is a common indicator of lipid peroxidation of the cellular membrane (37).…”

Alcoholic fatty liver disease inhibited the co-expression of Fmo5 and PPARα to activate the NF-κB signaling pathway, thereby reducing liver injury via inducing gut microbiota disturbance

“…In ammation induces the production of free radicals or decreases the ability of the body to scavenge free radicals, thus prompting the body to release a large amount of ROS [28]. ROS can further activate in ammatory response by activating NF-κB signal pathway [29]. The results of animal experiments show that Fmo5 and PPARα expression in small intestine and liver tissues of mice with AFLD decreased signi cantly and the apoptosis-related protein (cleaved caspase-3), phospho-NF-κB p65, and in ammation-associated cytokines (IL-6 and TNFα) in in small intestine and liver tissues of mice with AFLD increased signi cantly.…”