Sanvidhan G. Suke

Organochlorine pesticide residue levels and oxidative stress in preterm delivery cases

A number of studies have focused attention on various biochemical abnormalities evoked due to exposure to organochlorine pesticides (OCPs). The aim of the present study was to analyze the OCP residues in maternal and cord blood of women and assess the levels of different non-enzymatic oxidative stress markers as well as to establish correlation with OCP levels, if any. Thirty women in each group of full-term delivery (FTD; ≥37 weeks of gestation) and preterm delivery (PTD; <37 weeks of gestation) were enrolled in this study. Levels of OCPs like Hexachlorocyclohexane (HCH), endosulfan, p,p′ Dichlorodiphenyldichloroethylene (DDE) and p,p’ Dichlorodiphenyltrichloroethane (DDT) were analyzed by gas chromatography. Non-enzymatic oxidative stress was measured by the quantification of malondialhyde (MDA), protein carbonyl, reduced glutathione (GSH) and ferric-reducing ability of plasma (FRAP). MDA and protein carbonyl levels were increased significantly, while the levels of GSH and FRAP were decreased in PTD in comparison to FTD cases. We have observed higher levels of β-HCH and α-endosulfan and increased oxidative stress in PTD than FTD cases. In PTD cases, a significant positive correlation was observed between maternal blood levels of β-HCH and MDA (r = .78), β-HCH and GSH (r = —.65), γ-HCH and MDA (r = .89), γ-HCH and GSH (r = —.74) and α-endosulfan and MDA (r = .54) in PTD cases. We also found significant correlations between cord blood levels of β-HCH and MDA (r = .59), β-HCH and GSH (r = —.69), γ-HCH and MDA (r = .62) and α-endosulfan and MDA (r = .54) in PTD cases. In conclusion, our results suggest that higher levels of some of the OCP residues may be associated with PTD and increased oxidative stress.

Endosulfan and Other Organochlorine Pesticide Residues in Maternal and Cord Blood in North Indian Population

Humans are exposed to various environmental chemicals such as organochlorine pesticide residues, heavy metals, polychlorinatedbiphenyls (PCBs) etc. There is paucity of data regarding the present blood levels of organochlorine residues in North Indian population with reference to reproductive health. The present study was designed to analyze the levels of organochlorine pesticide residues in maternal and cord blood samples of normal healthy women with full term pregnancy to gain insight into the current status of pesticide burden in newborns. Hexachlorocyclohexane (HCH) contributed maximum towards the total organochlorine residues present in maternal and cord blood followed by endosulfan, pp′ DDE and pp′ DDT being the least. This is also the first report indicating endosulfan levels in this population. Our data indicates a transfer rate of 60–70% of these pesticides from mothers to newborns and this high rate of transfer of pesticides is of great concern as it may adversely affect the growth and development of newborn.

Protective effects of dietary ginger (Zingiber officinales Rosc.) on lindane-induced oxidative stress in rats.

The protective effect of dietary feeding of Zingiber officinales Rosc. (ginger) against lindane‐induced oxidative stress was investigated in male albino rats. Oxidative stress was monitored by estimating the extent of lipid peroxidation, activities of the oxygen free radical (OFR) scavenging enzymes superoxide dismutase (SOD) and catalase (CAT) and the status of the glutathione redox cycle antioxidants. Lindane administration (30 mg/kg bw orally for 4 weeks) was associated with enhanced lipid peroxidation and compromised antioxidant defenses in rats fed a normal diet. Concomitant dietary feeding of ginger (1%w/w) significantly attenuated lindane‐induced lipid peroxidation, accompanied by modulation of OFR scavenging enzymes as well as reduced glutathione (GSH) and the GSH dependent enzymes glutathione peroxidase (Gpx), glutathione reductase (GR) and glutathione‐S‐transferase (GST) in these rats. These findings suggest that a diet containing naturally occurring compounds is effective in exerting protective effects by modulating oxidative stress. Copyright

Endosulfan-induced apoptosis and glutathione depletion in human peripheral blood mononuclear cells: Attenuation by N-acetylcysteine.

Present study investigated whether endosulfan, an organochlorine pesticide is able to deplete glutathione (GSH) and induce apoptosis in human peripheral blood mononuclear cells (PBMC) in vitro. The role of oxidative stress in the induction of apoptosis was also evaluated by the measurement of the GSH level in cell lysate. The protective role of N‐acetylcysteine (NAC) on endosulfan‐induced apoptosis was also studied. Isolated human PBMC were exposed to increasing concentrations (0–100 µM) of endosulfan (α/β at 70:30 mixture) alone and in combination with NAC (20 µM) up to 24 h. Apoptotic cell death was determined by Annexin‐V Cy3.18 binding and DNA fragmentation assays. Cellular GSH level was measured using dithionitrobenzene. Endosulfan at low concentrations, i.e., 5 and 10 µM, did not cause significant death during 6 h/12 h incubation, whereas a concentration‐dependent cell death was observed at 24 h. DNA fragmentation analysis revealed no appreciable difference between control cells and 5 µM/10 µM endosulfan treated cells, where only high molecular weight DNA band was observed. Significant ladder formation was observed at higher concentration, which is indicative of apoptotic cell death. Intracellular GSH levels decreased significantly in endosulfan‐treated cells in a dose‐dependent manner, showing a close correlation between oxidative stress and degree of apoptosis of PBMC. Cotreatment with NAC attenuated GSH depletion as well as apoptosis. Our results provide experimental evidence of involvement of oxidative stress in endosulfan‐mediated apoptosis in human PBMC in vitro.

Role of HSP27 and reduced glutathione in modulating malathion-induced apoptosis of human peripheral blood mononuclear cells: ameliorating effect of N-acetylcysteine and curcumin.

Malathion exerts cholinergic effects at high doses. However, a consequence of low dose (non-cholinergic) exposure causes immunotoxicity and oxidative stress. Hence, this study was designed to find out (i) the cytotoxic and apoptotic effects of cholinergic and non-cholinergic doses of malathion using cultured peripheral blood mononuclear cells (PBMCs) and (ii) the role of GSH and HSP27 and (iii) protective effects of N-acetylcysteine (GSH inducer) and curcumin (HSP27 inducer). In low doses, malathion caused mild depletion of GSH, threefold increase in HSP27 level and a range bound cytotoxicity and apoptosis of PBMC. In contrast, cholinergic dose exposures caused severe GSH depletion and exhibited dose dependent cytotoxicity and necrosis without any significant effect on HSP27 levels. Curcumin increased the levels of HSP27 in PBMC only in presence of low doses and not at high doses of malathion. Both NAC and curcumin were able to prevent malathion-mediated apoptosis of PBMC effectively at non-cholinergic doses and at this concentration of malathion, HSP27 induction keeps apoptosis and GSH depletion under control. Also NAC and curcumin may act as potential therapeutic agents to prevent malathion-induced immunotoxicity.

Ameliorative effect of nanoencapsulated flavonoid against chlorpyrifos-induced hepatic oxidative damage and immunotoxicity in Wistar rats

The theme of the present work is to evaluate the protective effect of nanoencapsulated quercetin (NEQ) against chlorpyrifos (CPF)‐induced hepatic damage and immune alterations in animals. Nanoparticles (NP) drug encapsulation was prepared. Forty male Wistar rats were divided into eight groups. Two groups served as control and CPF (13.5 mg/kg) treatment for 28 days. Other three groups were free quercetin (QC), NP and NEQ treated with 3 mg/kg respectively for 15 days; whereas remaining three groups received treatment of CPF and QC, NP, NEQ, respectively, for 15 days. The results show that significantly altered oxidative stress in the liver tissue and liver enzyme parameters in blood and immune responses in CPF‐treated rats compared to controls. Administration of NEQ attenuated biochemical and immunological parameters. The liver histopathological analysis confirmed pathological improvement. Hence, use of NEQ appeared to be beneficial to a great extent in attenuating and restoring hepatic oxidative damage and immune alteration sustained by pesticide exposure.

Alteration of superoxide- and nitric oxide-mediated antimicrobial function of macrophages by in vivo cocaine exposure.

Cocaine is a popular drug of abuse and despite impressive advances in the understanding of its physiological, pharmacological, and toxic effects, its mechanism of immunosuppression at the cellular level is not well understood. In this paper we report the role of effector molecules like superoxide and nitric oxide in the antibacterial function of macrophages exposed to acute and chronic doses of cocaine in vivo. Bacterial killing by acute cocaine-exposed macrophages (ACE-Mphis) increased significantly, with a concomitant rise in respiratory burst and generation of superoxide and nitric oxide, compared with control macrophages. In contrast, chronic cocaine-exposed macrophages (CCE-Mphis) exhibited limited antimicrobial activity, which correlated closely with diminished respiratory burst and reduced production of superoxide and nitric oxide. Further, a killing assay was carried out in the presence of N(G)-methyl-L-arginine acetate, an inhibitor of iNOS, to evaluate the role of nitric oxide in the killing process. The results obtained indicate that while about 30% killing of input bacteria by control and ACE-Mphis was attributable to NO-mediated killing, only about 6% killing from NO was found with CCE-Mphis. The findings indicate that acute exposure to cocaine possibly caused upregulation of enzymes responsible for the generation of ROI (reactive oxygen intermediates) and RNI (reactive nitrogen intermediates), leading to enhanced antimicrobial function. On the other hand, chronic exposure to cocaine impaired the oxygen-dependent microbicidal capacity of macrophages, possibly through impaired expression of enzymes responsible for ROI and RNI formation. Proinflammatory cytokines may play a key role in cocaine-mediated immunosuppression, since exposure of macrophages to cocaine impairs the ability of the cells to produce these cytokines.