Effect of acute exposure of triazophos on oxidative stress and histopathological alterations in liver, kidney and brain of Wistar rats.

Acute dose of organophosphorus pesticide Triazophos (O,O-diethyl O-1-phenyl-1H-1,2,4-triazol-3-yl phosphorothioate; Tz) administered orally affects oxidative stress parameters and the histo-architecture of liver, kidney and brain tissues. The results indicate a dose dependent induction of oxidative stress as evident by increased malondialdehyde level and decreased antioxidant defense including glutathione and superoxide dismutase activity in rat liver, kidney and brain. AChE activity was found significantly decreased in the Tz treated groups as compared to the vehicle control (DMSO) group. Histopathological examination of liver, kidney and brain in Tz treated rats revealed medullary congestion and hydropic degeneration of hepatocytes in liver and medullary congestion in kidney. However, no significant histopathological changes were observed in brain tissues.

Megazol and its bioisostere 4H-1,2,4-triazole: comparing the trypanocidal, cytotoxic and genotoxic activities and their in vitro and in silico interactions with the Trypanosoma brucei nitroreductase enzyme

Megazol (7) is a 5-nitroimidazole that is highly active against Trypanosoma cruzi and Trypanosoma brucei, as well as drug-resistant forms of trypanosomiasis. Compound 7 is not used clinically due to its mutagenic and genotoxic properties, but has been largely used as a lead compound. Here, we compared the activity of 7 with its 4H-1,2,4-triazole bioisostere (8) in bloodstream forms of T. brucei and T. cruzi and evaluated their activation by T. brucei type I nitroreductase (TbNTR) enzyme. We also analysed the cytotoxic and genotoxic effects of these compounds in whole human blood using Comet and fluorescein diacetate/ethidium bromide assays. Although the only difference between 7 and 8 is the substitution of sulphur (in the thiadiazole in 7) for nitrogen (in the triazole in 8), the results indicated that 8 had poorer antiparasitic activity than 7 and was not genotoxic, whereas 7 presented this effect. The determination of Vmax indicated that although 8 was metabolised more rapidly than 7, it bounds to the TbNTR with better affinity, resulting in equivalent kcat/KM values. Docking assays of 7 and 8 performed within the active site of a homology model of the TbNTR indicating that 8 had greater affinity than 7.

Induction of oxidative stress and histopathological changes by sub-chronic doses of triazophos.

The effect of triazophos (O, O-diethyl O-1-phenyl-1 H-1, 2, 4-triazol-3-yl phosphorothioate), a widely used insecticide was studied on the induction of oxidative stress and histological alterations at sub-chronic doses in male albino rats. Oral administration of triazophos at concentrations of 1.64, 3.2 and 8.2 mg/kg body wt for 30 days produced dose as well as time-dependent increase in the lipid peroxidation (determined by malondialdehyde levels) and glutathione-S-transferase (GST) activity in serum with a concomitant decrease in ferric reducing ability of plasma (FRAP) and blood glutathione (GSH) content. Histopathological examination of liver of triazophos-treated rats showed significant and progressive degenerative changes as compared to control, which could be due to induction of oxidative stress. However, no significant histopathological changes were observed in spleen, kidney and brain at either dose of triazophos with respect to control. These results indicated that oral administration of triazophos was associated with enhanced lipid peroxidation and compromised antioxidant defence in rats in dose and time-dependent manner. Thus the present study demonstrated for the first time the role of oxidative stress as the important mechanism involved in the stimulation of hepatic histo-architectural alterations at sub-chronic doses of triazophos in rats.

Oral toxicity of agro-fungicides: tilt [propiconazole], bayleton [triadimefon] and their mixture to nubian goats

The hazard use of pesticides, emergence of many diseases with high prevalence e. g [cancer, kidney failure and hepatic problems] urged the need for research on fungicides which are continuously received by human in Sudan via fruit and vegetables. To detect the toxicity of these fungicides in experimental animals. Twelve Nubian goats were used in these experiments; they were grouped into three groups [and one control group] and dosed orally with two fungicides [Propiconazole [100 mg/kg/day], Triadimefon [100mg/kg/day]] and their mixture [50:50 mg/kg/day]. Animals were closely observed for clinical signs and behavior. Dead or slaughtered animals underwent postmortem examination and lesions were recorded. Samples from different organs were preserved for histopathological studies. Fresh blood was collected for heamatological and Serobiochemical analysis. Five minutes post-dosing, the animals showed some clinical signs which recovered after four hours. Death occurred in days 12-25 in the animals dosed with the mixture. The most prominent feature in postmortem lesions was the congestion in different organs. Histopathological changes were the fatty change of liver and kidneys. In Triadimefon dosed group, the values of PCV, Hb and MCHC decreased significantly [p<0.001]. The serum urea concentration and GOT activity were high [p<0.001] in both of them. Animals dosed with mixture had significantly [p<0.05-0.001] higher PCV, MCV, MCH and WBC than the control. Significantly high values of serum urea concentration [p<0.01] and GOT activity [p<0.001] were reported in goats dosed with the mixture. Both fungicides and their mixture showed toxicological and pathological effects in dosed animals

Pre-clinical toxicity of IDPH-791: a new centrally acting muscle relaxant in rats.

IDPH-791, a novel centrally acting muscle relaxant, in doses up to 500 mg/kg (po) for 14 days did not result in any appreciable adverse effect on body weight gain, food or water consumption including biochemical and haematologica parameters in rats. Variations observed in the biochemistry and haematology were either comparable to controls or were within normal limits.