Pharmacotherapeutic effects of kumatakenin against cadmium-induced cardiotoxicity in rats via suppression of oxidative stress, inflammation, and apoptosis: Role of Nrf2/HO-1 and TLR4/MyD88/TRAF6/NF-κB signaling pathways.
TL;DR
Overall, KM showed promising therapeutic properties against Cd-instigated cardiotoxicity in rats via restoring antioxidant status as well as suppressing inflammation and apoptosis.
Abstract
Background
Cadmium (Cd) is an extremely toxic, non-essential heavy metal associated with cardiac toxicity. Kumatakenin (KM) is a naturally occurring flavonoid that exhibits potent pharmacological properties. Therefore, this investigation aimed to examine the cardioprotective effects of KM to counteract Cd-induced toxicity in cardiac tissues of rats.
Methods
For the experiment, 48 adult albino rats were divided into four groups as follows: control, Cd-treated (5 mg/kg), Cd + KM (5 mg/kg + 25 mg/kg) co-treated, and KM-only (25 mg/kg) treated group. Biochemical analysis was performed through standard assays and ELISA whereas qRT-PCR was used to quantify the mRNA expression.
Results
Outcomes of this study revealed that Cd-treatment suppressed Nrf2/HO-1 antioxidant pathway, which led to the reduced activity of antioxidant enzymes (GSR, CAT, GPx, and SOD), whereas elevated the level of reactive oxygen species (ROS) and malondialdehyde (MDA). In addition, Cd-exposure increased the levels of cardiac injury parameters, including creatine kinase-MB (CK-MB), troponin-I, creatine phosphokinase (CPK), and lactate dehydrogenase (LDH). Moreover, the expressions of TLR4, MyD88, TRAF6, and NF-κB were upregulated in response to Cd treatment, which led to increased secretion of pro-inflammatory cytokines i.e., tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), and interleukin-1 beta (IL-1β). Furthermore, Cd intoxication upregulated Bax and caspase-3 gene expressions and downregulated the expressions of Bcl-2 while elevating histopathological anomalies. However, co-treatment with KM ameliorated all these abnormalities and significantly restored myocardial architecture owing to its antioxidant, anti-inflammatory and anti-apoptotic properties.
Conclusion
Overall, KM showed promising therapeutic properties against Cd-instigated cardiotoxicity in rats via restoring antioxidant status as well as suppressing inflammation and apoptosis.