cyhalothrin and Inflammation

λ-Cyhalothrin, a type II synthetic pyrethroid, has been widely used in households, agriculture, public health, and gardening to control insect pests. Despite its widespread usage, it is known to induce a variety of adverse effects, including hepatotoxicity and nephrotoxicity. The goal of this study was to investigate the protective effect of carvacrol, which has antioxidant, anti-inflammatory, anti-apoptotic, and some other properties, on λ-Cyhalothrin-induced hepatotoxicity and nephrotoxicity 35 male Sprague-Dawley rats were randomly divided into five groups for this purpose: I-Control group: II-CRV group (50 mg/kg carvacrol), III-LCT group (6.23 mg/kg LCT), IV-LCT + CRV 25 group (6.23 mg/kg LCT + 25 mg/kg carvacrol), and V-LCT + CRV 50 group (6.23 mg/kg LCT + 50 mg/kg carvacrol). Using biochemical, real-time PCR, and western blotting methods, the collected tissues were analyzed. While λ-Cyhalothrin treatment increased MDA levels, which are indicated of lipid peroxidation, but reduced SOD, CAT, GPx activities, and GSH levels. After receiving carvacrol therapy, the degree of oxidative stress reduced as the values of these parameters approached those of the control group. Increased inflammation, apoptosis, endoplasmic reticulum stress, and autophagy with λ-Cyhalothrin administration reduced with carvacrol co-administration, and liver and kidney tissues were protected from damage, depending on the degree of oxidative stress. After considering all of these data, it was discovered that λ-Cyhalothrin-induced oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress, and autophagy in the liver and kidneys; however, carvacrol protected the tissues from damage. Our findings indicate that carvacrol may be a promising protective agent in λ-Cyhalothrin-induced hepatotoxicity and nephrotoxicity.

Topics: Animals; Apoptosis; Autophagy; Chemical and Drug Induced Liver Injury; Endoplasmic Reticulum Stress; Inflammation; Insecticides; Male; Oxidative Stress; Pyrethrins; Rats; Rats, Sprague-Dawley

The risk to develop neurobehavioural abnormalities in humans on exposure to lambda-cyhalothrin (LCT) - a type II synthetic pyrethroid has enhanced significantly due to its extensive uses in agriculture, homes, veterinary practices and public health programs. Earlier, we found that the brain dopaminergic system is vulnerable to LCT and affects motor functions in rats. In continuation to this, the present study is focused to unravel the role of neuroinflammation in LCT-induced neurotoxicity in substantia nigra and corpus striatum in rats. Increase in the mRNA expression of proinflammatory cytokines (TNF- α, IL-1β, IL-6) and iNOS whereas decrease in anti-inflammatory cytokine (IL-10) was distinct both in substantia nigra and corpus striatum of rats treated with LCT (0.5, 1.0, 3.0 mg/kg body weight, p.o, for 45 days) as compared to control rats. Further, LCT-treated rats exhibited increased levels of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1), the glial marker proteins both in substantia nigra and corpus striatum as compared to controls. Exposure of rats to LCT also caused alterations in the levels of heat shock protein 60 (HSP60) and mRNA expression of toll-like receptors (TLR2 and TLR4) in the substantia nigra and corpus striatum. An increase in the phosphorylation of key proteins involved in NF-kβ (P65, Iκβ, IKKα, IKKβ) and JAK/STAT (STAT1, STAT3) signaling and alteration in the protein levels of JAK1 and JAK2 was prominent in LCT-treated rats. Histological studies revealed damage of dopaminergic neurons and reactive gliosis as evidenced by the presence of darkly stained pyknotic neurons and decrease in Nissl substance and an increase in infiltration of immune cells both in substantia nigra and corpus striatum of LCT-treated rats. Presence of reactive microglia and astrocytes in LCT-treated rats was also distinct in ultrastructural studies. The results exhibit that LCT may damage dopaminergic neurons in the substantia nigra and corpus striatum by inducing inflammation as a result of stimulation of neuroglial cells involving activation of NF-κβ and JAK/STAT signaling.

Topics: Animals; Corpus Striatum; Cytokines; Dopaminergic Neurons; Humans; Inflammation; Pyrethrins; Rats; RNA, Messenger; Substantia Nigra; Tumor Necrosis Factor-alpha

The present study aims to elucidate the molecular basis of lambda cyhalothrin (LCT) toxicity. Thirty-two mature male albino rats were randomly classified into four equal groups. The first group was orally administered normal saline, the second group was orally administered dimethylsulfoxide (DMSO). The third group was orally administered 1/100 LD50 (6.12 mg/kg b. wt) of a commercial formulation containing 2.5% LCT (i.e., a net dose LCT corresponding to 0.15 mg/kg b. wt). The fourth group was orally administered 1/100 LD50 (0.64 mg/kg b. wt) of a pure form of LCT. The results indicated that exposure to LCT is capable of inducing an up-regulation in the mRNA expression levels of peroxisome proliferative activated receptor α and γ (PPAR α and PPAR γ), tumor necrosis factor (TNF-α), fatty acid synthase (FAS) and sterol regulatory element binding protein-1c (SREBP-1c). Additionally, our study revealed a significant increase in serum levels of ALT, AST, ALP, γGT as well as the inflammatory cytokines TNF-α and monocyte chemoattractant protein-1 (MCP-1). A significant elevation in total lipids, total cholesterol, triacylglycerol, LDL-c and leptin with a corresponding significant decrease in HDL-c was also noted. Moreover, our results depicted that LCT treatment exhibits a significant increase in hepatic MDA levels concurrent with a significant decrease in GSH levels and the activities of CAT, SOD, and GPx. An immunohistochemical investigation also revealed a strong up-regulation of hepatic FAS in the LCT treated groups. The histopathological findings were marked by evidence in support of periportal fatty changes and interstitial aggregation of round cells.

Topics: Animals; Antioxidants; Fungicides, Industrial; Gene Expression Regulation; Inflammation; Lipogenesis; Liver; Male; Nitriles; Oxidation-Reduction; Pyrethrins; Rats; Rats, Wistar