Excessive alcohol consumption is a global healthcare problem with enormous social, economic, and clinical consequences. While chronic, heavy alcohol consumption causes structural damage and/or disrupts normal organ function in virtually every tissue of the body, the liver sustains the greatest damage. This is primarily because the liver is the first to see alcohol absorbed from the gastrointestinal tract via the portal circulation and second, because the liver is the principal site of ethanol metabolism. Alcohol-induced damage remains one of the most prevalent disorders of the liver and a leading cause of death or transplantation from liver disease. Despite extensive research on the pathophysiology of this disease, there are still no targeted therapies available. Given the multifactorial mechanisms for alcohol-associated liver disease pathogenesis, it is conceivable that a multitherapeutic regimen is needed to treat different stages in the spectrum of this disease.

Methotrexate (MTX) is an immunosuppressant used for the treatment of cancer and autoimmune diseases. MTX has a major adverse effect, acute kidney injury, which limits its use. Mangiferin (MF) is a natural bioactive xanthonoid used as a traditional herbal supplement to boost the immune system due to its potent anti-inflammatory and antioxidant activity. The present study evaluates the protective effect of MF against MTX-induced kidney damage. Male Wistar rats received MTX to induce nephrotoxicity or were pretreated with MF for 10 constitutive days before MTX administration. MF dose-dependently improved renal functions of MTX-treated rats and this activity was correlated with increased renal expression of PPARγ, a well-known transcriptional regulator of the immune response. Pretreating rats with PPARγ inhibitor, BADGE, reduced the reno-protective activity of MF. Furthermore, MF treatment significantly reduced MTX-induced upregulation of the pro-inflammatory (NFκB, interleukin-1ß, TNF-α, and COX-2), oxidative stress (Nrf-2, hemoxygenase-1, glutathione, and malondialdehyde), and nitrosative stress (nitric oxide and iNOS) markers in the kidney. Importantly, BADGE treatment significantly reduced the anti-inflammatory and antioxidant activity of MF. Therefore, our data suggest that the reno-protective effect of MF against MTX-induced nephrotoxicity is due to inhibition of inflammation and oxidative stress in a PPAR-γ-dependent manner.

Temephos, an organophosphate insecticide, is widely accepted for the control of Aedes aegypti, vector of infectious diseases such as dengue, chikungunya, yellow fever, and zika. However, there are claims that repeated and indiscriminate use of temephos has resulted in resistance development in exposed mosquito populations. The present study attempts to evaluate the continuous performance of temephos on the Ae. aegypti population, in laboratory conditions, in terms of toxicity and the effect on marker enzymes associated with metabolic resistance. Results of the toxicity bioassay showed that after the initial exposure, toxicity increased till F4 generation by 1.65 fold, and continuous exposure resulted in a 7.83 fold reduction in toxicity at F28 generation. Percent mortality result showed a marked reduction in mortality with the passage of generations while using the same series of concentrations, viz. 2 ppm, which was 100 % lethal at the initial nine generations, could kill only 22.66 % at F28. Resistance to organophosphates is mainly governed by metabolic detoxifying enzyme families of esterases, glutathione-s-transferase, and cytochrome P450. Analysis of these metabolic detoxifying enzymes showed an inverse trend to toxicity (i.e. toxicity increased in early generations as enzyme activity dropped and then dropped as enzyme activity increased). At the initial exposure, enzyme activity decreased in 2-4 generations, however, repeated exposure led to a significant increase in all the metabolic detoxifying enzymes. From the toxicity level as well as marker enzyme bioassay results, it can be inferred that mosquitoes showed increased detoxification in generational time with an increase in enzymes associated with metabolic detoxification. In conclusion, repeated application of temephos led to resistance development in Ae. aegypti which may be associated with the increase in metabolic detoxifying enzyme activities.

Earlier reports have shown that Cyclophosphamide (CYCP), an anti-malignant drug, elicited cytotoxicity; and that naringin has several beneficial potentials against oxidative stress and dyslipidaemias. We investigated the influence of naringin on free radical scavenging, cellular integrity, cellular ATP, antioxidants, oxidative stress, and lipid profiles in the CYCP-induced erythrocytotoxicity rat model. Rats were pretreated orally by gavage for fourteen consecutive days with three doses (50, 100, and 200 mg/kg) naringin before single CYCP (200 mg/kg, i.p.) administration. Afterwards, the rats were sacrificed. Naringin concentrations required for 50 % scavenging hydrogen peroxide and nitric oxide radical were 0.27 mg/mL and 0.28 mg/mL, respectively. Naringin pretreatment significantly (p < 0.05) protected erythrocytes plasma membrane architecture and integrity by abolishing CYCP-induced decrease in the activity of erythrocyte LDH (a marker of ATP). Pretreatment with naringin remarkably (p < 0.05) reversed CYCP-induced decreases in the erythrocytes glutathione levels, activities of glutathione-S-transferase, catalase, glutathione peroxidase, and glutathione reductase; attenuated CYCP-mediated increases in erythrocytes levels of malondialdehyde, nitric oxide, and major lipids (cholesterol, triacylglycerol, phospholipids, and non-esterified fatty acids). Taken together, different acute pretreatment doses of naringin might avert CYCP-mediated erythrocytes dysfunctions via its antioxidant, free-radical scavenging, and anti-dyslipidaemia properties.

OBJECTIVE: In the present study, we investigate the phytochemical composition and the nephroprotective effects as well as the antioxidant properties of Artemisia herba alba aqueous extract in alloxan-induced experimental diabetes in rats.
METHODS: Wistar rats were divided into four groups of seven rats each: Group I: Normal control (NC) received saline solution at 9‰ given by intraperitoneal way; Group II: Diabetic control (DC) received alloxan (150 mg/kg b.w) intraperitoneally; Group III: Normal control (NC + AHA) received saline solution at 9‰ and treated orally by AHA aqueous extract (400 mg/kg/b.w); Group IV: Diabetic control (DC + AHA) received alloxan solution (150 mg/kg b.w) intraperitoneally and treated by aqueous extract of AHA (400 mg/kg/b.w/day) orally after one week of alloxan administration. After 30 days, blood and tissue samples were collected for biochemical and histopathological analysis, respectively. Glomerular damage markers, including creatinine, serum urea, urine creatinine and urine urea levels were estimated. Creatinine clearance was also assessed. Oxidative stress parameters were assessed in the kidney homogenate.
CONCLUSIONS: Alloxan-exposure resulted in significant increase in blood glucose and serum level of glomerular damage markers. The antioxidant enzyme activities were significantly downregulated associated with an increase in malondialdehyde (MDA) level over the baseline values. Artemisia herba alba aqueous extract supplementation significantly improved the studied parameters. In concluding, the results obtained suggests that Artemisia herbs-alba aqueous extract supplementation reduces alloxan-induced free radical generation, potentiates the antioxidant defense system and alleviates renal sensitivity to oxidative stress.

Phenylhydrazine (PHZ), an intermediate in the synthesis of fine chemicals is toxic for human health and environment. Despite of having severe detrimental effects on different physiological systems, exposure of erythrocytes to PHZ cause destruction of haemoglobin and membrane proteins leading to iron release and complete haemolysis of red blood cells (RBC). Involvement of oxidative stress behind such action triggers the urge for searching a potent antioxidant. The benefits of consuming olive oil is attributed to its 75% oleic acid (OA) content in average. Olive oil is the basic component of Mediterranean diet. Hence, OA has been chosen in our present in vitro study to explore its efficacy against PHZ (1 mM) induced alterations in erythrocytes. Four different concentrations of OA (0.01 nM, 0.02 nM, 0.04 nM and 0.06 nM) were primarily experimented with, among which 0.06 nM OA has shown to give maximal protection. This study demonstrates the capability of OA in preserving the morphology, intracellular antioxidant status and the activities of metabolic enzymes of RBCs that have been diminished by PHZ, through its antioxidant mechanisms. The results of the present study firmly establish OA as a promising antioxidant for conserving the health of erythrocyte from PHZ toxicity which indicate toward future possible use of OA either singly or in combination with other dietary components for protection of erythrocytes against PHZ induced toxic cellular changes.

The physiological and metabolic processes of host plants are manipulated and remodeled by phytopathogenic fungi during infection, revealed obvious signs of biotrophy of the hemibiotrophic pathogen. As we known that effector proteins play key roles in interaction of hemibiotrophic fungi and their host plants. BAS4 (biotrophy-associated secreted protein 4) is an EIHM (extrainvasive hyphal membrane) matrix protein that was highly expressed in infectious hyphae. In order to study whether BAS4 is involved in the transition of rice blast fungus from biotrophic to necrotrophic phase, The susceptible rice cultivar Lijiangxintuanheigu (LTH) that were pre-treated with prokaryotic expression product of BAS4 and then followed with inoculation of the blast strain, more serious blast disease symptom, more biomass such as sporulation and fungal relative growth, and lower expression level of pathogenicity-related genes appeared in lesion of the rice leaves than those of the PBS-pretreated-leaves followed with inoculation of the same blast strain, which demonstrating that BAS4 invitro changed rice defense system to facilitate infection of rice blast strain. And the susceptible rice cultivar (LTH) were inoculated withBAS4-overexpressed blast strain, we also found more serious blast disease symptom and more biomass also appeared in lesion of leaves inoculated with BAS4-overexpressed strain than those of leaves inoculated with the wild-type strain, and expression level of pathogenicity-related genes appeared lower in biotrophic phase and higher in necrotrophic phase of infection, indicating BAS4 maybe in vivo regulate defense system of rice to facilitate transition of biotrophic to necrotrophic phase. Our data demonstrates that BAS4 in vitro and in vivo participates in transition from the biotrophic to the necrotrophic phase of Magnaporthe oryzae.

BACKGROUND: This is a case-control study aimed at evaluating clinical as well as molecular risk factors for occurrence of ATT induced hepatitis in Northern Indian population.
METHODS: 100 patients of tuberculosis were recruited from both Outdoor patient department and wards of Lok Nayak Hospital, New Delhi. 40 out of 100 patients who developed ATT induced hepatitis were taken as test group and 60 out of 100 patients who didn\'t develop liver dysfunction on ATT were taken as controls and studied and compared for clinical factors such as age, gender, nutritional status, HBsAg carrier, chronic hepatitis C and HIV infection. Molecular factors i.e. NAT2 acetylator status, GSTT1 and M1 null mutations were also determined in all of the patients in each group and compared.
RESULTS: Mean body weight and serum albumin were significantly lower in the ATT induced hepatitis patients as compared to the control group. No preferential association was observed between age and gender with ATT induced hepatitis. HBsAg carrier (OR-6.5; P = 0.03), HIV infection (OR-5.1; P = 0.01), slow acetylator phenotype (OR-3.85; P = 0.02), GSTM1 null mutation (OR-2.72; P = 0.02) and GSTT1 null mutation (OR-3.12; P = 0.02) were found to be positively co-related to ATT induced hepatitis according to the univariate analysis. HBsAg carrier (OR-23.18; P = 0.01), HIV infection (OR-16.92; P = 0.02), Slow acetylator phenotype (OR-70.90; P = 0.001), GSTM1 null mutation (OR-37.03; P = 0.002) and GSTT1 null mutation (OR-8.19; P = 0.014) were also found to be independently increasing the risk of ATT induced hepatitis using multivariate analysis.
CONCLUSIONS: The present study established a positive co-relation between malnutrition, HBsAg carrier, HIV infection, NAT2 slow acetylators, GSTM1 null mutation, GSTT1 null mutation and ATT induced hepatitis.

Lambda-cyhalothrin (LCT) is a synthetic pyrethroid that is widely used to control insecticide. Ginger is a traditional plant that is widely used as a spice or folk medicine. This study evaluates the antioxidant effect of ginger extract on thyroid toxicity induced by LCT in albino rats. Adult Rats were divided into 4 experimental groups: Group 1: control, Group 2: oral ginger treatment (24 mg/ml, 3 days/week for 4 weeks), Group 3: oral LCT treatment (1/100 LD50, 3 days/week for 4 weeks), Group 4: oral LCT and ginger mixture treatment. The histological results of LCT group showed degenerated follicles with reduced colloids, congestion of blood vessels and hyperaemia between the follicles. Histochemically, depletion of glycogen and proteins was recorded in follicular cells and colloids. The biochemical results of LCT treated group revealed a decrease in T3, T4, SOD and CAT, while TSH and MDA were increased. The comet assay showed that LCT significantly induced DNA damage in the thyroid gland. However, treating rats with LCT plus ginger led to an improvement in the histological structure of the thyroid, with noticeable increases in glycogen and protein deposition. Also, LCT plus ginger increase in T3, T4 and the antioxidant enzymes SOD and COT were detected concomitantly with a decrease in TSH and MDA as well as a significant reduction in DNA damage. LCT affected the thyroid function and structure. On the other hand, ginger has a preventative effect against the histological damage and biochemical toxicity caused by the (LCT) insecticide.

The present study investigated the possible protective role of Withania somnifera (Linn.) Dunal (Solanaceae) root powder against bromobenzene-induced oxidative damage in rat liver mitochondria. Administration of bromobenzene (10 mmol/kg body weight) to rats resulted in increased levels of liver marker enzymes, lipid peroxidation, TNF-α, IL-1β and VEGF. There was also marked depletion in the levels of mitochondrial enzymes and antioxidant activity. Pre-treatment with W. somnifera significantly decreased the levels of liver marker enzymes, TNF-α, IL-1β, VEGF and ameliorated histopathological manifestations in bromobenzene-treated rats. The molecular docking analysis predicted that the pro-inflammatory mediator NF-κB showed significant interaction with selected various active components of W. somnifera (withaferin A, withanolide D and withanolide E). This study demonstrates a good protective effect of W. somnifera against bromobenzene-induced oxidative stress.