Psoriatic Nephropathy and its Correlation with hs-CRP: A Case Control Study.

BACKGROUND: Psoriasis is a multisystem disorder associated with various systemic diseases such as cardiovascular diseases, diabetes mellitus and metabolic syndrome. Renal involvement in patients with psoriasis is sparsely studied and its association is still unclear. AIM: The aim of this article was to study causal attributable renal involvement in patients with psoriasis and factors affecting the same. METHODS: Fifty patients with documented psoriasis were recruited after excluding any secondary causes of renal disease. They were subjected to routine investigations along with hs-CRP and specific investigations for kidney function including urine albumin creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). The eGFR and ACR of the patients were compared with 50 age- and sex-matched controls. Association with any disease-related factors such as severity and duration were assessed. Renal biopsy was planned in patient with ACR >500 mg/g creatinine. RESULTS: The mean eGFR (IQR) (ml/min/1.73 m2) of the case group was found to be 80.00 (71.00-95.75) and in the control group was 88.00 (75.25-99.00). This difference was not significant (P = 0.206). However, in the age group of > 30 years, the eGFR of disease group (78.50 ± 17.94) was significantly lower than that in the control group (88.96 ± 17.01, P = 0.023).The mean urine ACR (mg/g) in the disease group was found to be 13.359 ± 26.01 while that in the control group was found to be 5.66 (3.40-8.08), and the difference was not found to be clinically significant. Four patients with psoriasis had microalbuminuria as opposed to none of the controls. CONCLUSION: Subclinical albuminuria was found in 8 per cent of patients with psoriasis. Glomerular dysfunction with statistically significant reduction in eGFR was seen in psoriasis in age group of more than 30 years and those who had a long-standing disease. The renal involvement had positive correlation with hs-CRP indicating the role of inflammatory milieu. Further large-scale cohort studies would help assess this aspect in further details. LIMITATION OF THE STUDY: Sample size was small. Large-scale studies would be required to further substantiate these observations.

Effect of Low-Intensity Microwave Radiation on Monoamine Neurotransmitters and Their Key Regulating Enzymes in Rat Brain.

The increasing use of wireless communication devices has raised major concerns towards deleterious effects of microwave radiation on human health. The aim of the study was to demonstrate the effect of low-intensity microwave radiation on levels of monoamine neurotransmitters and gene expression of their key regulating enzymes in brain of Fischer rats. Animals were exposed to 900 MHz and 1800 MHz microwave radiation for 30 days (2 h/day, 5 days/week) with respective specific absorption rates as 5.953 × 10(-4) and 5.835 × 10(-4) W/kg. The levels of monoamine neurotransmitters viz. dopamine (DA), norepinephrine (NE), epinephrine (E) and serotonin (5-HT) were detected using LC-MS/MS in hippocampus of all experimental animals. In addition, mRNA expression of key regulating enzymes for these neurotransmitters viz. tyrosine hydroxylase (TH) (for DA, NE and E) and tryptophan hydroxylase (TPH1 and TPH2) (for serotonin) was also estimated. Results showed significant reduction in levels of DA, NE, E and 5-HT in hippocampus of microwave-exposed animals in comparison with sham-exposed (control) animals. In addition, significant downregulation in mRNA expression of TH, TPH1 and TPH2 was also observed in microwave-exposed animals (p < 0.05). In conclusion, the results indicate that low-intensity microwave radiation may cause learning and memory disturbances by altering levels of brain monoamine neurotransmitters at mRNA and protein levels.

Protective effect of melatonin on propoxur-induced impairment of memory and oxidative stress in rats.

Propoxur (a carbamate pesticide) has been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. This study was designed to explore the modulation of the effects of propoxur over cognitive function by melatonin (MEL). Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus, and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining brain malondialdehyde (MDA) and reduced glutathione (GSH) levels and catalase (CAT) activity. A significant reduction in SDL and prolongation of TL was observed for the propoxur (10 mg/kg/d; p.o.) treated group at weeks 6 and 7 when compared with control. One week treatment with MEL (50 mg/kg/d; i.p.) antagonized the effect of propoxur on SDL, as well as TL. Propoxur produced a statistically significant increase in the brain MDA levels and decrease in the brain GSH levels and CAT activity. Treatment with MEL attenuated the effect of propoxur on oxidative stress. The results of the present study thus show that MEL has the potential to attenuate cognitive dysfunction and oxidative stress induced by toxicants like propoxur in the brain.

Increased level of organochlorine pesticides in chronic kidney disease patients of unknown etiology: role of GSTM1/GSTT1 polymorphism.

Chronic kidney disease (CKD) of unknown etiology represents about 16% of CKD patients in Indian subcontinents and 10% worldwide. The aetiology of CKD of unknown etiology remains unclear though epidemiological studies indicate the involvement of the environmental toxins. Organochlorine pesticides (OCPs) have been detected in general population in India. It is possible that polymorphism of xenobiotic metabolizing enzymes (XMEs) may play an important role in this process. In this we intend to find out blood levels of OCPs in CKD patients of unknown etiology and to evaluate the consequence of glutathione S-transferase (GST) gene polymorphism on the same. We have assessed 270 CKD patients and 270 age-sex-matched healthy controls for this study. The blood OCP levels were analyzed by gas chromatograph. GSTM1, GSTT1 genotyping were carried out by multiplex PCR. Blood levels of HCH, endosulfan and total pesticides were significantly higher in CKD patients and negatively correlated with eGFR. The combined frequency of GSTM1(-)/GSTT1(-) genotype increased the risk of CKD by 1.8-fold as compared to healthy controls. To find out the dependence of blood OCPs level on genotype, we carried out logistic regression analysis and results revealed that GSTM1(-)/GSTT1(-) genotype associated significantly with a number of OCPs namely γ-HCH, p,p'-DDT and total pesticides. Polymorphism of XMEs not only increased accumulation of pesticides but also aggravates kidney dysfunction as evident from significant decrease in eGFR.

Pulmonary function and oxidative stress in workers exposed to styrene in plastic factory: occupational hazards in styrene-exposed plastic factory workers.

Styrene is a volatile organic compound used in factories for synthesis of plastic products. The pneumotoxicity of styrene in experimental animals is known. The aim of the present study was to study the effect of styrene on lung function and oxidative stress in occupationally exposed workers in plastic factory. Thirty-four male workers, between 18 and 40 years of age, exposed to styrene for atleast 8 hours a day for more than a year were studied, while 30 age- and sex-matched healthy subjects not exposed to styrene served as controls. Assessment of lung functions showed a statistically significant reduction (p < 0.05) in most of the lung volumes, capacities (FVC, FEV(1), VC, ERV, IRV, and IC) and flow rates (PEFR, MEF(75%), and MVV) in the study group (workers) as compared to controls. Malondialdehyde (MDA) was observed to be significantly high (p < 0.05) while ferric-reducing ability of plasma (FRAP) was significantly low (p < 0.05) in styrene-exposed subjects. Reduced glutathione (GSH) level was significantly depleted in exposed subjects as compared to control group. The mean value of serum cytochrome c in styrene-exposed subjects was found to be 1.1 ng/ml (0.89-1.89) while in control its levels were under detection limit (0.05 ng/ml). It shows that styrene inhalation by workers leads to increased level of oxidative stress, which is supposed to be the cause of lung damage.

Effect of progesterone on phosphamidon-induced impairment of memory and oxidative stress in rats.

Progesterone (a neurosteroid) is an important modulator of the nervous system functioning. Organophosphorus pesticides like phosphamidon have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. The present study was therefore designed to investigate the effects of progesterone (PROG) on phosphamidon-induced modulation of cognitive function and oxidative stress in rats. Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of thiobarbituric acid reactive species (TBARS) and non-protein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and prolongation of TL in the phosphamidon (1.74 mg/kg/d; p.o.) treated group at weeks 6 and 8 as compared to the control group. Two weeks treatment with PROG (15 mg/kg/d; i.p.) antagonized the effect of phosphamidon on SDL as well as TL. Phosphamidon alone produced a significant increase in the brain TBARS levels and decrease in the brain NP-SH levels. Treatment with PROG (15 mg/kg/d; i.p.) attenuated the effect of phosphamidon on oxidative stress. Together, the results showed that progesterone attenuated the cognitive dysfunction and increased oxidative stress induced by phosphamidon in the brain.

Ameliorating effect of N-acetylcysteine and curcumin on pesticide-induced oxidative DNA damage in human peripheral blood mononuclear cells.

Endosulfan, malathion, and phosphamidon are widely used pesticides. Subchronic exposure to these contaminants commonly affects the central nervous system, immune, gastrointestinal, renal, and reproductive system. There effects have been attributed to increased oxidative stress. This study was conducted to examine the role of oxidative stress in genotoxicity following pesticide exposure using peripheral blood mononuclear cells (PBMC) in vitro. Further possible attenuation of genotoxicity was studied using N-acetylcysteine (NAC) and curcumin as known modulators of oxidative stress. Cultured mononuclear cells was isolated from peripheral blood of healthy volunteers, and exposed to varying concentrations of different pesticides: endosulfan, malathion, and phosphamidon for 6, 12, and 24 h. Lipid peroxidation was assessed by cellular malondialdehyde (MDA) level and DNA damage was quantified by measuring 8-hydroxy-2'-deoxyguanosine (8-OH-dG) using ELISA. Both MDA and 8-OH-dG were significantly increased in a dose-dependent manner following treatment with these pesticides. There was a significant decrease in MDA and 8-OH-dG levels in PBMC when co-treated with NAC or/and curcumin as compared to pesticide alone. These results indicate that pesticide-induced oxidative stress is probably responsible for the DNA damage, and NAC or curcumin attenuate this effect by counteracting the oxidative stress.

Assessment of phosphamidon-induced apoptosis in human peripheral blood mononuclear cells: protective effects of N-acetylcysteine and curcumin.

The molecular mechanism for noncholinergic toxicity of phosphamidon, an extensively used organophosphate pesticide, is still not clear. The aim of the present study is to find the possible molecular mechanism of this pesticide to induce apoptosis and the role of different drugs for attenuation of such effects. Human peripheral blood mononuclear cells (PBMC) were incubated with increasing concentrations of phosphamidon (0-20 µM) for 6-24 h. The MTT assay reveals that phosphamidon induces cytotoxicity in a dose-dependent manner. Cellular glutathione (GSH) is depleted in a dose-dependent manner from 55% to 70% at concentrations between 10 and 20 µM. The percentage of cells that bind to Annexin-V, which is a representative of cells either undergoing apoptosis or necrosis during 24 h incubation, increases in a dose-dependent manner. Above 5 µM, significant necrosis of cells was observed. DNA fragmentation assay revealed that at low concentration of phosphamidon (1 µM), no appreciable change in DNA fragmentation was seen; however, distinct fragmentation was observed beyond 2.5 µM. Phosphamidon was found to cause significant depletion of GSH, which correlates well with the percentage of cells undergoing apoptosis. An increasing trend in levels of cytochrome c was observed with increasing concentration of phosphamidon, indicating that the apoptotic effect of phosphamidon is mediated through cytochrome c release. Coadministration of the antioxidants N-acetylcysteine and curcumin attenuated phosphamidon-induced apoptosis. This further supports our hypothesis that oxidative stress, as indicated by GSH depletion, results in the induction of apoptosis by release of cytochrome c.

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.

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 microM) of endosulfan (alpha/beta at 70:30 mixture) alone and in combination with NAC (20 microM) 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 microM, 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 microM/10 microM 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.

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.