Investigation of molecular effects of beta caryophyllene in cadmium-induced nephrotoxicity model in rats: in silico and in vivo studies.

Background

Cadmium is one of the toxic heavy metals that accumulate in the kidneys, and it can cause kidney damage by triggering oxidative stress, ER stress, inflammation, and apoptosis. β-caryophyllene (BCP) is a volatile ingredient found in various spice essential oils, known for its anti-inflammatory and strong oxygen-free radical scavenging properties. In this study, we aimed to test the effects of BCP on kidney damage caused by Cd administration.

Methods

Adult male Sprague Dawley (n = 35) were divided to the five following groups (n = 7/group): control group, BCP group that received BCP intragastric for 7 days (400 mg/kg/day), Cd group that received CdCl2 intraperitoneal injections for 7 days (6.5 mg/kg/day), and rats that received Cd simultaneously with small (200 mg/kg/day) and high doses (400 mg/kg/day) of BCP.

Results

BCP significantly reduced lipid peroxidation, restored reduced glutathione (GSH), superoxide dismutase (SOD) levels and catalase activity, decreased the elevations of Toll-like receptor 4 (TLR-4), nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), IL-1β in cadmium-induced kidney injury. Histopathological examination showed that cadmium-induced kidney injury was attenuated by BCP treatment. Immunohistochemical and immunofluorecence analysis showed that BCP significantly decreased the cadmium-induced overexpression of Keap-1, Bax, and caspase-3, increased the cadmium-induced downexpression of Bcl-2, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in kidney tissues. BCP also markedly mitigated ER stress (GRP78, ATF4, ATF6, and CHOP expressions).

Conclusion

Thus, BCP may protect kidney tissues from Cd-induced nephrotoxicity by regulating oxidant/antioxidant status, reducing inflammation, ER stress, cell death, and activating the Nrf2/HO-1 signaling pathway.