ABSTRACT
Acetamiprid, a selective agonist of nicotinic acetylcholine recetors, is one of the most widely used neonicotinoids. There is limited data about toxicity of acetamiprid on male reproductive system. Therefore, the study aimed to investigate the reproductive toxic potential of acetamiprid in male rats orally treated with acetamiprid with low (12.5 mg/kg) medium (25 mg/kg) or high dose (35 mg/kg) for 90 days. According to our results, sperm concentration and plasma testosterone levels decreased in dose dependent manner. Gonadotropin-releasing hormone (GnRH), follicle-stimulating hormeone (FSH), luteinizing hormone (LH) levels increased at low and medium dose groups and acetamiprid caused lipid peroxidation and glutathione (GSH) depletion in the testes. Histologic examinations revealed that acetamiprid induced apoptosis in medium and high dose groups and proliferation index dramatically decreased in high dose group. In conclusion, acetamiprid caused toxicity on male reproductive system in the high dose. The mechanism of the toxic effect may be associated with oxidative stress, hormonal disruptions and apoptosis.
Subject(s)
Genitalia, Male/drug effects , Genitalia, Male/metabolism , Insecticides/toxicity , Neonicotinoids/toxicity , Sperm Count , Administration, Oral , Animals , Dose-Response Relationship, Drug , Glutathione/metabolism , Gonadotropin-Releasing Hormone/blood , Lipid Peroxidation , Luteinizing Hormone/blood , Male , Neonicotinoids/administration & dosage , Rats, Sprague-Dawley , Testis/metabolism , Testosterone/bloodABSTRACT
BACKGROUND/OBJECTIVE: The present study investigated the potent therapeutic effects of Ruscogenin, main steroid sapogenin of traditional Chinese plant called 'Ophiopogon japonicas', on chronic ulcer model established with acetic acid in rats. METHODS: 24 rats were attenuated to the sham (2 ml/kg/day isotonic solution), control (untreated ulcer) and treatment (3 ml/kg/day ruscogenin) groups. After treatment for 2 weeks, gastric tissues were collected and prepared for light microscopic (H&E), immunohistochemical (Collagen I, III and IV) and biochemical analysis [Epidermal growth factor (EGF), Prostaglandin E2 (PGE2), Tumor Necrosis Factor alpha (TNF-α), Interleukin 6 and 8 (IL-6 and IL-8), Lipid Peroxidase (LPO), Myeloperoxidase (MPO), Glutathione (GSH) and Glutathione Peroxidase (GSH-Px)] and transmission electron microscopy (TEM). RESULTS: Macroscopic scoring showed that the ulceration area of ruscogenin-treated group decreased compared with control group. Immunohistochemical analysis revealed ruscogenin ameliorated and restored the levels of Collagen I and IV to the levels of sham group. Tissue levels of EGF and PGE2 enhanced significantly in untreated ulcer group while were higher in treated ulcer group than the control group. TNF-α, IL-6, IL-8, LPO, MPO levels increased significantly in control group whereas decreased in treated rats after ruscogenin treatment. However, levels of GSH and GSH-Px increased significantly in treatment group. TEM showed chief cells and parietal cells of ulcer group having degenerated organelles while ruscogenin group had normal ultrastructure of cells. CONCLUSION: There are potent anti-inflammatory and anti-oxidant effects of ruscogenin on gastric ulcer and may be successfully used as a safe and therapeutic agent in treatment of peptic ulcer.
Subject(s)
Phytotherapy , Spirostans/administration & dosage , Stomach Ulcer/drug therapy , Animals , Chronic Disease , Collagen/metabolism , Cytokines/metabolism , Dinoprostone/metabolism , Disease Models, Animal , Epidermal Growth Factor/metabolism , Female , Microscopy, Electron, Transmission , Ophiopogon/chemistry , Parietal Cells, Gastric/pathology , Parietal Cells, Gastric/ultrastructure , Peroxidases/metabolism , Rats, Sprague-Dawley , Spirostans/isolation & purification , Stomach Ulcer/metabolism , Stomach Ulcer/pathology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
PURPOSE: To determine the potential protective and therapeutic effects and action mechanism of ruscogenin on cerulein-induced acute pancreatitis (AP) model in rats. METHODS: Overall, 32 rats were attenuated to the sham (2-mL/kg/day isotonic solution for 4 weeks), control (20-µg/kg cerulein-induced AP for 12 hours), prophylaxis groups (cerulein-induced AP following 3-mL/kg/day ruscogenin for 4 weeks) and treatment (3-mL/kg/day ruscogenin following cerulein-induced AP for 12 hours). Blood samples were collected for biochemical analysis of nitric oxide synthase 1 (NOS1/neuronal NOS), malondialdehyde (MDA) and intercellular adhesion molecule 1 (ICAM-1). After sacrification, pancreas tissues were collected and prepared for light microscopic (hematoxylin and eosin), immunohistochemical (nuclear factor kappa B) and biochemical analysis (tumor necrosis factor-alpha [TNF-α], interleukin-6 and 1ß [IL-6 and IL-1ß], CRP, high-sensitivity CRP [hs-CRP] amylase, lipase, and ICAM-1). Ultrastructural analysis was performed by transmission electron microscopy. RESULTS: The protective and therapeutic actions of ruscogenin were accomplished by improvements in histopathology, by decreasing blood cytokine levels of CRP, hs-CRP levels, TNF-α, IL-6, IL-1ß, ICAM-1, by reducing the pancreatic enzymes amylase and lipase in blood, and by suppressing the expression of nuclear factor kappa B, ICAM-1, and NOS-1, but not MDA in pancreatic tissues. Ruscogenin also improved cerulein-induced ultrastructural degenerations in endocrine and exocrine cells, especially in treatment group. CONCLUSION: The present findings have demonstrated the beneficial protective and therapeutical effects of ruscogenin, nominating it as a highly promising supplementary agent to be considered in the treatment of AP, and even as a protective agent against the damages induced by disease.
