NOPR Collection: Special issue on Environmental Pollution and Experimental Pharmacological Approaches

Sub-chronic arsenic exposure aggravates nephrotoxicity in experimental diabetic rats

2010-06-12T16:30:47Z

Title: Sub-chronic arsenic exposure aggravates nephrotoxicity in experimental diabetic rats Authors: Patel, Hitesh Vashrambhai; Kalia, Kiran Abstract: The present experiment was planned to study nephrotoxicity in experimental diabetic rats under sub-chronic exposure to arsenic. Alloxan induced diabetic and control rats were exposed to sodium arsenite (0 and 5.5 mg/kg, orally) for 30 days. More pronounced nephrotoxic effects were noted in arsenic exposed diabetic group as evidenced by increased blood urea nitrogen, serum creatinine and relative kidney weight and decreased level of reduced glutathione and glutathione peroxidase activity compared to non arsenic exposed diabetic group. Increased level of lipid peroxidation, protein oxidation, superoxide dismutase and catalase activities under diabetic condition remained unchanged in arsenic exposed diabetic group compared to unexposed diabetic group. Page(s): 762-768

Prophylactic efficacy of combination of DRDE-07 and its analogues with amifostine against sulphur mustard induced systemic toxicity

2010-06-13T16:30:41Z

Title: Prophylactic efficacy of combination of DRDE-07 and its analogues with amifostine against sulphur mustard induced systemic toxicity Authors: Gautam, Anshoo; Gupta, Alka; Lomash, Vinay; Pant, S C; Vijayaraghavan, R Abstract: Sulphur mustard, [bis (2-chloroethyl)] sulphide (SM), is a bifunctional alkylating agent. SM forms sulphonium ion in the body which alkylates DNA and several other macromolecules, and induces oxidative stress. Although several antidotes have been screened for the treatment of systemic toxicity of SM in experimental animals none of them are recommended so far. In the search for more effective and less toxic antidotes, various combinations were tried against SM induced toxicity and skin lesions. SM exposed through percutaneous route was used to evaluate the prophylactic efficacy of various combinations. Low dose of DRDE-07 (S-2(2-aminoethylamino) ethyl phenyl sulphide), DRDE-30 [S-2(2-aminoethyl amino) ethyl propyl sulphide], DRDE-35 [S-2(2-aminoethyl amino) ethyl butyl sulphide] with amifostine combinations, were given orally 30 min prior to SM exposure. Significant depletion was observed in body weight, organ body weight index and hepatic GSH and GSSG content in mice after SM exposure. Pretreatment with low dose of different combinations of DRDE-07, DRDE-30 and DRDE-35 with amifostine could recover biochemical alterations and histopathological changes caused by SM exposures. Page(s): 752-761

Acute and sub-acute toxicity of an insect pheromone, N-heneicosane and combination with insect growth regulator, diflubenzuron, for establishing no observed adverse effect level (NOAEL)

2010-06-12T16:30:46Z

Title: Acute and sub-acute toxicity of an insect pheromone, N-heneicosane and combination with insect growth regulator, diflubenzuron, for establishing no observed adverse effect level (NOAEL) Authors: Bhutia, Yangchen Doma; Jain, Neeti; Ahmed, Fakhruddin; Sharma, Manoj; Singh, Ram; Kumar, Satish; Mendki, Murlidhar Jaywantrao; Kumar, Pravin; Vijayaraghavan, R Abstract: Aedes aegypti mosquito is one of the most notorious vectors of dangerous diseases like dengue hemorrhagic fever and chikangunya. One method of control of the vectors is by the use of semiochemicals or pheromones. The pheromone n-heneicosane (C21) has been proved to be effective in attracting the female Aedes aegypti to lay eggs in the treated water and the growth of the larva is controlled by insect growth regulator diflubenzuron (DB). This study was planned to assess the safety of C21 alone and the combination with DB. Acute toxicity tests were carried out using two doses, viz., 1600 and 3200 mg/kg and two routes of exposure oral and intra-peritoneal. Dermal toxicity test was carried out in both male and female rats at the dose of 3200 mg/kg. Primary skin irritation test was carried out in rabbits. Sub-acute (90 days) dermal toxicity studies in male and female rats at the dose of 1 and 2 mg/kg via the per-cutaneous route were also studied. Sub-acute (90 days) toxicity test through the oral route was carried out, at doses 125, 250 and 500 mg/kg in male and female rats. The calculated LD₅₀ by ip route and dermal route was more than 5 g/kg in mouse and rats of both the sexes. In the primary skin irritation test no significant changes were noted. In the sub-acute toxicity studies even 500 mg/kg dose was not able to produce toxic response in rats when they were dosed daily for 90 days. The established no observed adverse effect level (NOAEL) was more than 500 mg/kg. Page(s): 744-751

Microsomal Ca²⁺ flux modulation as an indicator of heavy metal toxicity

2010-06-11T16:30:49Z

Title: Microsomal Ca²⁺ flux modulation as an indicator of heavy metal toxicity Authors: Pentyala, Srinivas; Ruggeri, Jeanine; Veerraju, Amulya; Yu, Zhangzhang; Bhatia, Anjori; Desaiah, Durisala; Vig, Parminder Abstract: Inositol 1,4,5-trisphosphatee (IP3), an intracellular messenger, releases Ca²⁺ from microsomes. Ca²⁺ plays a major role in regulating various cellular events like neural transmission and regulation of hormones and growth factors. Aluminum (Al), lead (Pb) and mercury (Hg) were reported to alter Ca²⁺-regulated events thereby causing neurotoxicity. Hence, an attempt was made characterize IP3 mediated Ca²⁺ release from rat brain microsomes under the influence of Al, Pb and Hg. Different concentrations of metals were tested over a designated time scale and their effects on IP3 mediated Ca²⁺ release from microsomes were monitored using Fura-2 technique. All the three metals inhibited IP3 mediated Ca²⁺ release, Pb being more potent. The order of potency of these three metals was Pb>Hg>Al. Except for Al, both Hg and Pb independently released Ca²⁺ from microsomes. Re-uptake of Ca²⁺ into microsomes was inhibited by all the three metals, Pb being more potent. Microsomal Ca²⁺-ATPase activity was also inhibited by all the three metals. These results suggest that neurotoxicity exerted by Al, Pb and Hg may be due to the interference of these metals with IP3 mediated calcium release and also interfering with the microsomal Ca²⁺ sequestration mechanism. Differential effects of heavy metal induced changes in Ca²⁺ flux can be used as an index of relative toxicity. Page(s): 737-743

NOPR Collection: Special issue on Environmental Pollution and Experimental Pharmacological Approaches

Sub-chronic arsenic exposure aggravates nephrotoxicity in experimental diabetic rats

Prophylactic efficacy of combination of DRDE-07 and its analogues with amifostine against sulphur mustard induced systemic toxicity

Acute and sub-acute toxicity of an insect pheromone, N-heneicosane and combination with insect growth regulator, diflubenzuron, for establishing no observed adverse effect level (NOAEL)

Microsomal Ca2+ flux modulation as an indicator of heavy metal toxicity

Microsomal Ca²⁺ flux modulation as an indicator of heavy metal toxicity