Perfluorooctane sulfonate‐induced apoptosis in kidney cells by triggering the NOX4/ROS/JNK axis and antagonism of cannabidiol

Abstract

Perfluorooctane sulfonate (PFOS) is one of the persistent organic pollutants (POPs), which can cause severe nephrotoxicity in mammals. Cannabinol (CBD), a nonpsychoactive cannabinoid obtained from the cannabis plant, has attracted attention in recent years for its excellent antioxidant properties. NADPH oxidase 4 (NOX4) has an important effect in supporting normal renal physiological function. The potential mechanisms of PFOS nephrotoxicity and whether CBD can prevent renal damage caused by PFOS remain unclear. This work aimed to study the mechanisms of PFOS‐induced kidney damage and the protective role of CBD against PFOS‐induced kidney damage. We demonstrated that PFOS led to renal insufficiency and structural damage in mice, induced overexpression of NOX4 and the onset of oxidative stress, and activated apoptosis of the mitochondrial pathway via the JNK signaling pathway. However, treatment with CBD reversed these changes. For further investigation of the potential mechanism of PFOS‐induced renal cell apoptosis, the expression of NOX4 was inhibited in vitro experiments using Apocynin, an effective NOX4 inhibitor. The outcomes showed that PFOS‐induced ROS production and JNK signaling pathway activation and apoptosis in human embryonic kidney (HEK293) cells were significantly reduced after inhibition of NOX4. This suggests that PFOS‐induced NOX4 overexpression serves as an upstream event for JNK pathway activation. In conclusion, the findings suggest that PFOS induces apoptosis in renal cells via the NOX4/ROS/JNK pathway. Meanwhile, CBD alleviated PFOS‐induced renal apoptosis through the inhibition of NOX4/ROS/JNK axis activation.

Selenium deficiency caused hepatitis in chickens via the miR-138-5p/SelM/ROS/Ca2+ overload pathway induced by hepatocyte necroptosis

“…Numerous studies have shown that tissue and organ damage due to selenium deficiency is closely related to oxidative stress. 52 In the present study, we found that the levels of CAT, SOD and GSH decreased while MDA, H 2 O 2 , TNOS and iNOS activities increased in chicken liver tissue and LMH cells after selenium deficiency. In addition, knockdown of SelM and overexpression of miR-138-5p increased the level of intracellular ROS, which was alleviated by NAC addition.…”

"Cannabinoids as Potential Therapeutic Agents for Kidney and Liver Toxicity: A Review"

“…The results of a study suggest that treatment with Δ -9-THC reduced kidney injury caused by ischemia-reperfusion injury and inflammation through the reducing oxidative stress in the kidney tissue [26]. In addition, Several studies have found that the ECS has a role in renal inflammation, oxidative stress, and fibrosis, which are key factors in nephrotoxicity development and progression [25,[27][28][29]. While the exact protective mechanisms of cannabinoids such as CBD, THC, as well as endocannabinoids against nephrotoxicity are not completely understood, it is believed that they produce this effect through various pathways that include promoting the regeneration of damaged cells in addition to the reduction of apoptosis, inflammation, and oxidative stress [28,29].…”

“…In addition, Several studies have found that the ECS has a role in renal inflammation, oxidative stress, and fibrosis, which are key factors in nephrotoxicity development and progression [25,[27][28][29]. While the exact protective mechanisms of cannabinoids such as CBD, THC, as well as endocannabinoids against nephrotoxicity are not completely understood, it is believed that they produce this effect through various pathways that include promoting the regeneration of damaged cells in addition to the reduction of apoptosis, inflammation, and oxidative stress [28,29]. Inflammation is one of the major factors contributing to renal disease, and various studies show that cannabinoids have anti-inflammatory effects.…”

Cadmium exposure induces necroptosis of porcine spleen via ROS‐mediated activation of STAT1/RIPK3 signaling pathway

“…Oxidative stress can lead to damages in the body. The ROS‐driven JNK signaling pathway was responsible for the induction of kidney apoptosis by Perfluorooctane sulfonate (Du et al, 2023). A study investigates lead‐induced kidney inflammation through ROS‐mediated MAPKs and NF‐κB pathway (Liu et al, 2012).…”