Alleviative effects of pinostrobin against cadmium-induced renal toxicity in rats by reducing oxidative stress, apoptosis, inflammation, and mitochondrial dysfunction

Abstract

IntroductionCadmium (Cd) is a highly toxic heavy metal that can be found everywhere in the environment and can have harmful effects on both human and animal health. Pinostrobin (PSB) is a bioactive natural flavonoid isolated from Boesenbergia rotunda with several pharmacological properties, such as antiinflammatory, anticancer, antioxidant, and antiviral. This investigation was intended to assess the therapeutic potential of PSB against Cd-induced kidney damage in rats.MethodsIn total, 48 Sprague Dawley rats were divided into four groups: a control, a Cd (5 mg/kg), a Cd + PSB group (5 mg/kg Cd and 10 mg/kg PSB), and a PSB group (10 mg/kg) that received supplementation for 30 days.ResultsExposure to Cd led to a decrease in the activities of catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX), whereas levels of reactive oxygen species (ROS) and malondialdehyde (MDA) increased. Cd exposure also caused a substantial increase in urea, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and creatinine levels. Moreover, a noticeable decline was noticed in creatinine clearance. Moreover, Cd exposure considerably increased the levels of inflammatory indices, including interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), nuclear factor kappa-B (NF-kB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) activity. Cd treatment decreased the expression of the antiapoptotic markers (Bcl-2) while increasing the expression of apoptotic markers (Bax and Caspase-3). Furthermore, Cd treatment substantially reduced the TCA cycle enzyme activity, such as alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and isocitrate dehydrogenase. Moreover, mitochondrial electron transport chain enzymes, succinatedehydrogenase, NADH dehydrogenase, cytochrome c-oxidase, and coenzyme Q-cytochrome reductase activities were also decreased following Cd exposure. PSB administration substantially reduced the mitochondrial membrane potential while inducing significant histological damage. However, PSB treatment significantly reduced Cd-mediated renal damage in rats.ConclusionThus, the present investigation discovered that PSB has ameliorative potential against Cd-induced renal dysfunction in rats.

Pinostrobin attenuates azoxymethane-induced colorectal cytotoxicity in rats through augmentation of apoptotic Bax/Bcl-2 proteins and antioxidants

“…Accordingly, numerous researchers have shown the antiradical potentials of PN in previously published reports. 33 , 60 , 61 Moreover, Ijaz et al 29 reported significant radical quenching activity of PN in cadmium-mediated oxidative stress in rats represented by an upsurge in the CAT, GSR, SOD and GSH-PX and down-modulation of MDA levels.…”

“…Accordingly, numerous researchers have shown the antiradical potentials of PN in previously published reports. 33,60,61 Moreover, Ijaz et al 29 reported significant radical quenching activity of PN in cadmium-mediated oxidative stress in rats represented by an upsurge in the CAT, GSR, SOD and GSH-PX and downmodulation of MDA levels. TNF-α is a well-documented pro-inflammatory cytokine that is released from monocytes and macrophages and is commonly secreted during the early stages of acute and chronic inflammatory diseases (colon cancer).…”

“…24 Pinostrobin (5-hydroxy-7-methoxy flavanone; PN) is a member of flavonoids and an ether (Figure 1) and a dietary bioflavonoid isolated from natural resources including plants, Pinus strobus, 4 Cajanus cajan (L.), 25 rhizomes of Boesenbergia rotunda 26 and finger root (Boesenbergia rotunda). 27 Numerous biological potentials exhibited by this flavanone including antioxidants, 28 anti-inflammatory, 29 augmentations of inflammatory cytokines (interleukin-1β, tumour necrosis factor (TNF)-α) 30 and anti-ulcerogenic actions. 26 Moreover, in vitro, studies revealed outstanding inhibitory efficacy of PN against the growth of breast cancer, 31 cervical, 32 lung cancers, 33 HL-60 and K562 leukaemia cells.…”

Luteolin alleviates cadmium-induced metabolism disorder through antioxidant and anti-inflammatory mechanisms in chicken kidney

“…COX-2 is an enzyme mediating the progression of inflammation ( Babar et al, 2024 ). Cd exposure mediated renal damage with considerably enhanced inflammatory indices, including IL-1β, TNF-α and IL-6, inducible COX-2 activity in rats ( Ijaz et al, 2023 ). So, our research results showed that Cd treatment markedly aggravated renal inflammatory damage evidenced by an increase in the IL-8, TNF-α, COX2 and IL-6 contents and protein expression levels in the chicken kidney.…”

Assessment of cooking methods and freezing on the nutritional value and health risks of heavy metals in four fish species consumed in Douala, Cameroon

“…The first favours atmospheric recycling, while the second lead to bioaccumulation in sediments and aquatic species. This bioaccumulation process leads to cumulative effects on the occurrence of biomagnification through the food chain [ 14 ] . Sea organisms accumulate these contaminants primarily by uptake through the skin and gills via surface contacts with sediments, industrial effluent, wastewater, as well as via the food they consume [ 15 ] .…”