Protective effect of rutin on acrylamide induced ovarian inflammation, oxidative stress, DNA damage, and hormonal changes: Based on in silico and in vivo study.

Acrylamide (AA) is a carcinogenic compound that affects people due to its frequent use in laboratories and industry as well as the high-temperature cooking of foods with high hydrocarbon content. AA is known to cause severe reproductive abnormalities. The main aim of this study is to evaluate the protective effect of rutin (RU), a phytoactive compound, against AA-induced reproductive toxicity in female rats. Initially, rats were exposed to AA (40 mg/kg for 10 days). Therapy of RU was given after AA intoxication consecutively for 3 days. After 24 h of the last treatment, all the animals were sacrificed. The study evaluated reproductive hormones, oxidative stress markers, membrane-bound enzymes, DNA damage, histological findings, and an in silico approach to determine the protective efficacy of RU. The results indicated that RU significantly protected against inflammation, oxidative stress, and DNA damage induced by AA, likely due to its antioxidant properties.

Biomimetic synthesis of silver nanoparticles for treatment of N-Nitrosodiethylamine-induced hepatotoxicity.

The development of bioengineered nanoparticles has attracted considerable universal attention in the field of medical science and disease treatment. Current studies were executed to evaluate the hepatoprotective activity of biosynthesized silver nanoparticles (AgNPs). Their characterization was performed by UV-Visible analysis, fourier transform infrared spectroscopy, transmission electron microscopy (TEM), scanning electron microscope (SEM), and Zeta analyses. In in vivo studies, albino rats (180 ± 10 g) were persuaded with model hepatic toxicant N-nitrosodiethylamine (NDEA) and subsequently cotreated with Morus multicaulis at 100 mg/kg and AgNPs at 100 µg/kg dose. NDEA administration elevates the levels of liver function test biomarkers, which were reinstated to normal by cotreatment of test drugs. The oxidative stress and concentration of drug-metabolizing enzyme increase after induction of toxicant (NDEA), these markers are restored toward normal after cotreatment of nano-drug. Treatments of M. multicaulis extract did not show such significant protection. The NDEA-treated groups showed a significant rise in the level of cytokines (interleukin [IL-6] and IL-10) and reached normal with subsequent treatment with AgNPs. Histopathological studies also exhibited the curative effect of AgNPs in the same manner. Thus current results strongly suggest that biomimetic AgNPs could be used as an effective drug against hepatic alteration.

Role of M.tuberculosis protein Rv2005c in the aminoglycosides resistance.

Tuberculosis is an airborne infectious disease caused by Mycobacterium tuberculosis which threatens the globe. Aminoglycosides {Amikacin (AK) & Kanamycin (KM)} are WHO recommended second-line anti-TB drugs used against the treatment of drug-resistant tuberculosis. Aminoglycosides target the steps of protein translation machinery of M.tuberculosis. Several mechanisms have been put forward to elucidate the phenomena of aminoglycosides resistance but our knowledge is still insufficient. The aim of the study was to understand the involvement of Mycobacterium tuberculosis universal stress protein (Rv2005c) in aminoglycosides resistance and virulence. To establish the relationship of universal stress protein Rv2005c with AK & KM resistance, Rv2005c was cloned, expressed in E.coli BL21 using pQE2 expression vector and antimicrobial drug susceptibility testing (DST) was carried out. STRING-10 was also used to predict the interacting protein partners of Rv2005c. DST showed that the minimum inhibitory concentration of induced recombinant cells (Rv2005c) were five and four folds shifted with AK and KM E-strips, respectively. STRING-10 showed the interacting protein partners of Rv2005c. Overexpression of Rv2005c leads to shifting in MIC which might be signifying its involvement in the survival/resistance of Mycobacteria by inhibiting/modulating the effects of AK and KM released from the E-strips. Interactome also suggests that Rv2005c and its interacting protein partners are cumulatively involved in M.tuberculosis resistance, stresses, and latency.

Identification of Cross Reactive Antigens of C. botulinum Types A, B, E & F by Immunoproteomic Approach.

Diseases triggered by microorganisms can be controlled by vaccines, which need neutralizing antigens. Hence, it is very crucial to identify extremely efficient immunogens for immune prevention. Botulism, a fatal neuroparalytic disease, is caused by botulinum neurotoxins produced by the anaerobic, Gram-positive spore-forming bacteria, Clostridium botulinum. Food-borne botulism and iatrogenic botulism are caused by botulinum toxin. Wound botulism, infant botulism, and adult intestinal botulism are caused by primarily C. botulinum followed by secondary intoxication. To identify protective antigens, whole cell proteome of C. botulinum type B was separated by two-dimensional gel electrophoresis. 2-D gel of whole cell proteins was probed with hyper immune sera of whole cell proteins of C. botulinum types A, E, and F. Six cross immunoreactive proteins were identified. These immunoreactive proteins will be further tested for developing vaccines and serodiagnostic markers against botulism.

Silver nanoparticles protect acetaminophen induced acute hepatotoxicity: A biochemical and histopathological approach.

The present study was premeditated to demonstrate the hepatoprotective effect of silver nanoparticles (AgNPs). Rats were treated with three different doses of AgNPs (50, 100 and 150 µg/kg, p.o.) after Acetaminophen (APAP; 2 g/kg, p.o. once only) intoxication. Treatment with AgNPs recouped the levels of serum aspartate amino transaminase (AST), alanine amino transaminase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), bilirubin, triglyceride (TG) and cholesterol in dose dependent manner. Significant reduction in lipid peroxidation (LPO) and restoration of reduced glutathione (GSH) was found in liver in AgNPs treated animals. Alleviated activities of adenosine triphosphatase (ATPase), glucose-6- phosphatase (G6Pase) and antioxidant enzymes viz. superoxide dismutase (SOD) and catalase (CAT) due to APAP induced toxicity in liver were recovered by the treatment of AgNPs. Improvement in histoarchitecture of liver was also consistent with biochemical observations. The results revealed that AgNPs showed significant dose-dependent protection against APAP induced hepatocellular injury.

M. tuberculosis ferritin (Rv3841): Potential involvement in Amikacin (AK) & Kanamycin (KM) resistance.

Tuberculosis is an infectious disease, caused by one of the most successful human pathogen, Mycobacterium tuberculosis. Aminoglycosides, Amikacin (AK) & Kanamycin (KM) are commonly used to treat drug resistant tuberculosis. They target the protein synthesis machinery by interacting with several steps of translation. Several explanations have been proposed to explain the mechanism of aminoglycoside resistance but still our information is inadequate. Iron storing/interacting proteins were found to be overexpressed in aminoglycosides resistant isolates. Iron assimilation and utilization in M. tuberculosis plays a crucial role in growth, virulence and latency. To establish the relationship of ferritin with AK & KM resistance ferritin (Rv3841/bfrB) was cloned, expressed and antimicrobial drug susceptibility testing (DST) was carried out. Rv3841/bfrB gene was cloned and expressed in E. coli BL21 using pQE2 expression vector. Etest results for DST against AK & KM showed that the minimum inhibitory concentration (MIC) of ferritin recombinant cells was changed. Recombinants showed two fold changes in MIC with AK and three fold with KM E-strips. Overexpression of ferritin reflect the MIC shift which might be playing a critical role in the survival of mycobacteria by inhibiting/modulating the effects of AK & KM. String analysis also suggests that ferritin interacted with few proteins which are directly and indirectly involved in M. tuberculosis growth, Iron assimilation, virulence, resistance, stresses and latency.

Toxicological effects of carbosulfan in rats: Antioxidant, enzymological, biochemical, and hematological responses.

Carbosulfan is often used in agriculture for pest control on crops and for treatment against pyrethroid-resistant mosquitoes. This study investigated the impact of carbosulfan on oxidative stress markers, antioxidant defense, hematological, biochemical, and enzymological parameters in Sprague Dawley rats. Rats were orally administered carbosulfan doses of 1.02 to 10.20 mg/kg body weight daily; after 96 h, blood samples were taken, and the liver, kidney, and brain were dissected out for study. Results indicate that carbosulfan significantly increased the levels of lipid peroxidation and suppressed the activity of reduced glutathione, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase, and adenosine triphosphatase. A mixed trend was observed in the activity of superoxide dismutase, while an increase was observed in the levels of serum uric acid, urea, aspartate aminotransferase, and alanine aminotransferase. Hemoglobin and albumin levels decreased but no significant differences were observed in creatinine and bilirubin levels. Future studies should include a more detailed analysis of the effects of chronic carbosulfan exposure on these biomarkers to further assess the impact of the pesticide on mammalian models.

Therapeutic efficacy of Nigella sativa Linn. seed extract against CCl4 induced hepatic injury in Wistar rats.

Carbon tetrachloride (CCl4) intake damages liver. We evaluated therapeutic potential of aqueous extract of Nigella sativa seeds against CCl4 induced liver damage in rats. The hepatic damage induced by CCl4 @ 1.5 mL/kg, ip was evidenced by a significant increase in the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, protein and urea lipid peroxidation (LPO) as well as reduction in hepatic antioxidant system e.g. reduced glutathione. Hepatic total protein and glucose-6-phosphatase activity were found decreased. Histological studies substantiated the above biochemical findings. However, after 48 h of administration of aqueous extract of N. sativa seeds (250, 500 and 750 mg/kg, po) it not only detoxified the toxicity but also reversed LPO, GSH, AST, ALT and serum protein changes at all the three doses. Both higher doses of extract were found effective in monitoring urea, albumin, total protein and G-6-Pase activity. However, on the basis of percent protection highest dose i.e., 750 mg/kg proved better. The result suggests that the aqueous extract of N. sativa seeds can be used as a hepatoprotective agent.

Co-administration of adjuvants along with Moringa oleifera attenuates beryllium-induced oxidative stress and histopathological alterations in rats.

CONTEXT: Moringa oleifera Lam. (Moringaceae) is a rich source of antioxidants. All parts of the plant are medicinally important and have been used as traditional medicine for a variety of human ailments in India. OBJECTIVE: Therapeutic efficacy of adjuvants with M. oleifera (MO) root extract was investigated against beryllium-induced oxidative stress. MATERIALS AND METHODS: Hydroalcoholic (50% v/v) root extract of M. oleifera (150 mg/kg, p.o.) alone and combinations of M. oleifera with either piperine (2.5 mg/kg, p.o.) or curcumin (5.0 mg/kg, p.o.) daily for 1 week were administered in experimental rats against beryllium toxicity (1.0 mg/kg, i.p. daily for 5 weeks). Oxidative stress parameters including blood sugar, G-6-Pase in liver, and DNA damage were analyzed. Histopathological changes in liver and kidney were also observed. RESULTS: Beryllium enhanced lipid peroxidation (LPO), depleted reduced glutathione (GSH) and antioxidant enzymes activities, decreased blood sugar and G-6-Pase activity, and did not damage DNA. Histologically, liver was observed with structural loss and disintegration of hepatocytes, heavy vacuolation in hepatocytes, and kidney was observed with constriction of glomeruli and hypertrophy in epithelial cells of uriniferous tubules. Therapy of M. oleifera with piperine was effective; however, combination of M. oleifera with curcumin showed better therapeutic effect by reduction of LPO, elevated GSH level, maintained antioxidant enzymes activities, restored blood sugar, and G-6-Pase activity in liver together with almost normal histoarchitecture of liver and kidney. DISCUSSION AND CONCLUSION: Curcumin enhanced therapeutic efficacy of M. oleifera root extract and showed better antioxidant potential against beryllium toxicity.

Methylmercury toxicity: amelioration by selenium and water-soluble chelators as N-acetyl cysteine and dithiothreitol.

The protective potential of chelators, i.e. N-acetyl cysteine (0.6 mg /kg, intraperitoneally) and dithiothreitol (15.4 mg kg(-1) , intraperitoneally) with selenium (0.5 mg kg(-1) , pre-oral) were evaluated individually and in combination against methylmercury-induced biochemical alterations and oxidative stress consequences. Forty-two male Sprague-Dawley rats were exposed with methylmercury (1.5 mg kg(-1) , pre-oral) daily for 21 days followed by different treatments for five consecutive days. Administration of methylmercury caused significant enhancement in the release of transaminases, alkaline phosphatases and lactate dehydrogenases in serum. A significant increased was observed in lipid peroxidation level with a concomitant decreased in glutathione content after methylmercury exposure in liver, kidney and brain. Hepatic microsomal drug metabolizing enzymes (aniline hydroxylase and amidopyrine N-demethylase) of cytochrome p4502E1 showed sharp depletion after methylmercury exposure. Alterations in histological changes in liver, kidney and brain were also noted in methylmercury administered group. All treated groups showed recovery pattern, but the combined treatments with N-acetyl cysteine and dithiothreitol in combination with selenium were more effective than that with either alone treatments in recovering blood biochemical changes after methylmercury toxicity. In conclusion, the results demonstrated that combination therapy may recover all blood biochemical alterations and offer maximum protection against methylmercury-induced toxicity.

Modulatory potential of Bacopa monnieri against aflatoxin B1 induced biochemical, molecular and histological alterations in rats.

Oxidative injury is concerned with the pathogenesis of several liver injuries, including those from acute liver failure to cirrhosis. This study was designed to explore the antioxidant activity of Bacopa monnieri (BM) on Aflatoxin B1 (AFB1) induced oxidative damage in Wistar albino rats. Aflatoxin B1 treatment (200 µg/kg/day, p.o.) for 28 days induced oxidative injury by a significant alteration in serum liver function test marker enzymes (AST, ALT, ALP, LDH, albumin and bilirubin), inflammatory cytokines (IL-6, IL-10 and TNF-α), thiobarbituric acid reactive substances (TBARS) along with reduction of antioxidant enzymes (GSH, SOD, CAT), GSH cycle enzymes and drug-metabolizing enzymes (AH and AND). Treatment of rats with B. monnieri (20, 30 and 40 mg/kg for 5 days, p.o.) after 28 days of AFB1 intoxication significantly restored these parameters near control in a dose-dependent way. Histopathological examination disclosed extensive hepatic injuries, characterized by cellular necrosis, infiltration, congestion and sinusoidal dilatation in the AFB1-treated group. Treatment with B. monnieri significantly reduced these toxic effects resulting from AFB1. B. monnieriper se group (40 mg/kg) did not show any significant change and proved safe. The cytotoxic activity of B. monnieri was also evaluated on HepG2 cells and showed a good percentage of cytotoxic activity. This finding suggests that B. monnieri protects the liver against oxidative damage caused by AFB1, which aids in the evaluation of the traditional usage of this medicinal plant.

The Open Pediatric Cancer Project.

Background: In 2019, the Open Pediatric Brain Tumor Atlas (OpenPBTA) was created as a global, collaborative open-science initiative to genomically characterize 1,074 pediatric brain tumors and 22 patient-derived cell lines. Here, we extend the OpenPBTA to create the Open Pediatric Cancer (OpenPedCan) Project, a harmonized open-source multi-omic dataset from 6,112 pediatric cancer patients with 7,096 tumor events across more than 100 histologies. Combined with RNA-Seq from the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA), OpenPedCan contains nearly 48,000 total biospecimens (24,002 tumor and 23,893 normal specimens). Findings: We utilized Gabriella Miller Kids First (GMKF) workflows to harmonize WGS, WXS, RNA-seq, and Targeted Sequencing datasets to include somatic SNVs, InDels, CNVs, SVs, RNA expression, fusions, and splice variants. We integrated summarized CPTAC whole cell proteomics and phospho-proteomics data, miRNA-Seq data, and have developed a methylation array harmonization workflow to include m-values, beta-vales, and copy number calls. OpenPedCan contains reproducible, dockerized workflows in GitHub, CAVATICA, and Amazon Web Services (AWS) to deliver harmonized and processed data from over 60 scalable modules which can be leveraged both locally and on AWS. The processed data are released in a versioned manner and accessible through CAVATICA or AWS S3 download (from GitHub), and queryable through PedcBioPortal and the NCI's pediatric Molecular Targets Platform. Notably, we have expanded PBTA molecular subtyping to include methylation information to align with the WHO 2021 Central Nervous System Tumor classifications, allowing us to create research- grade integrated diagnoses for these tumors. Conclusions: OpenPedCan data and its reproducible analysis module framework are openly available and can be utilized and/or adapted by researchers to accelerate discovery, validation, and clinical translation.

Oncofertility: Treatment options from bench to bedside.

In recent years, there has been continuous improvement in the treatment and diagnosis of cancer, which has led to a significant improvement in the survival rate of cancer patients. Treatments that include chemotherapy, radiotherapy, surgery, or combined therapy have several side effects that may lead to premature ovarian insufficiency in females or substantial male germ cell loss. Reproductive biologists recommend that all patients who are diagnosed with a malignant tumor must undergo a consultation for fertility protection and preservation. In this review, we discuss the background knowledge, methods, and options for fertility preservation and how these new strategies help oncologists, surgeons, pediatricians, and hematologists, conserve fertility and be aware of the concepts, methods, and importance of fertility guards. This review may aid in the advancement of novel personalized methods for fertility preservation according to patients' conditions.

Quercetin ameliorates acute acrylamide induced spleen injury.

Acrylamide is used for industrial and laboratory purposes; it also is produced during cooking of carbohydrate-rich food at high temperature. We investigated the therapeutic potential of quercetin for treatment of acute acrylamide induced injury to the spleen. We used female albino rats treated with acrylamide for 10 days followed by oral administration of quercetin in three doses for 5 days. We observed significantly reduced total body weight, spleen weight, red blood cells, total proteins, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phophate dehydrogenase, reduced glutathione, concentration of serum IgG and IgM after acrylamide induced toxicity compared to controls. We also found that white blood cells, triglycerides, cholesterol and lipid oxidation were increased significantly after acrylamide induced toxicity in rats compared to controls. Histoarchitecture of spleen was affected adversely by acrylamide toxicity. Administration of quercetin ameliorated adverse effects of acrylamide in a dose-dependent manner. Quercetin appears to ameliorate acrylamide induced injury to the spleen by increasing endogenous antioxidants and improving histoarchitecture and immune function.

Reversal of vanadium-induced toxicity by combination therapy of tiferron and α-tocopherol in rat during pregnancy and their fetuses.

OBJECTIVE: The aim of this study was to analyze the effect of tiferron (sodium 4, 5-dihydroxybenzene-1, 3-disulfonate) per se and combination with α-tocopherol against vanadium induced developmental toxicity. Vanadium, as vanadyl sulphate pentahydrate, was evaluated for embryotoxic/fetotoxic effect in female albino rats (Sprague Dawley). METHODS: The compound was administered by gavage to pregnant animals at a dose of 15 mg/kg/day, p.o. on day 6-15 of pregnancy (organogenesis). Tiferron was given on day 16-18 as chelating agent. Cesarean sections were performed on day 19 of gestation. RESULTS: Maternal toxicity was observed, the level of sugar in the blood decreased, while we observed an increase in serum protein, serum alkaline phosphatase and serum transaminase activity. Level of lipid peroxidation showed enhances value in fetal and maternal liver. Vanadium induced inhibition in glycogen contents. Protein contents were decreased in vital organs where as increased in uterus and placenta. There was increased activity of acid phosphatase with the concomitant decline in alkaline phosphatase, adenosine triphosphatase and succnic dehydrogenase after vanadium intoxication. Toxicant caused severe alteration in histopathological observation of maternal and fetal liver, kidney, uterus and placenta proving its toxic consequences at cellular level. Tiferron along with α-tocopherol dramatically reversed alterations of all variables towards control rather than individual treatment. CONCLUSION: The combination therapy of tiferron and α-tocopherol played a beneficial role in reducing vanadium induced developmental toxicity.

Evidences of the radiofrequency exposure on the antioxidant status, potentially contributing to the inflammatory response and demyelination in rat brain.

Present study exhibited the oxidative potential of microwave radiation (MWR) leading to the neurodegeneration in rats. Wistar rats were exposed at 2100 MHz frequency for 4 h/day, 5 days/week/3 months. Animals were exposed at an estimated specific absorption rate (0.453 W/kg) and power density (8.237 µW/m2). After exposure irradiated group was compared with control group. Results indicated that microwave exposure significantly increased the levels of serological triglycerides and cholesterol. Oxidative stress is observed through alteration of glutathione homeostasis followed by activated inflammatory response further confirmed by pro and anti-inflammatory cytokines in the exposed group. Histopathological assessments and electron microscopic observation confirmed a significant change in the myelination pattern and cellular organelles in the brain of exposed animals. Taking everything into account it can be concluded that chronic exposure of 2100-MHz frequency caused oxidative stress, which leads to neural damage and demyelination and may affect neural communication.

Defensive role of Nigella sativa against antituberculosis drugs induced renal toxicity.

Drug-induced nephrotoxicity is a common problem in clinical medicine and the frequency of drug-related acute and chronic kidney dysfunction worldwide. One of them is anti-tuberculosis (TB) drugs that cause renal function impairment during TB treatment. Medicinal plants contain bioactive compounds that are capable for treating drug or toxin-induced renal disorders. The aim of the present study was to assess the protective effect of the ethanolic extract of Nigella sativa seeds (NS) against anti-TB drugs (ATDs) induced nephrotoxicity in Wistar albino rats. Rats were treated with ATDs for 12weeks (3 alternative days in a week). Supplementation with 125mg NS/kg, p.o. was administered to the experimental rats for 12weeks (3 alternative days in a week considering next day of ATDs treatment). The results demonstrated that NS treatment protected against renal damage induced by ATDs, as evidenced by the reduction in serum urea, creatinine, uric acid, urea nitrogen levels, pro-inflammatory markers (TNF-α and IL-6), whereas improvement in histological tubular and glomerular damage. In addition, NS enhanced the antioxidant enzyme activity (superoxide dismutase and catalase) and decreased the lipid peroxidation and glutathione level in the kidney. In conclusion, NS could reduce chronic nephritis in ATDs treated group through suppressing inflammation and oxidative stress. It suggests that NS can be used as supplementary preventive and protective drug against kidney injury during anti-TB treatment.

Ameliorative impact of herbal formulation -Majoon-Dabeed-ul-ward and Sharbat-e-Deenar against CCl4 induced liver toxicity via regulation of antioxidant enzymes and oxidative stress.

Polyherbal Unani formulations have been used in the treatment of liver diseases for a long time. (Ibrahim M, Khaja MN, Aara A, Khan AA, Habeeb MA, Devi YP, Narasu ML, Habibullah CM. Hepatoprotective activity of Sapindus mukorossi and Rheum emodi extracts: in vitro and in vivo studies. World J Gastroenterol. 2008:14:2566-2571.) The aim of the present study was to investigate comparative hepatoprotective potential of Majoon-e-Dabeed-ul-ward (MD) and Sharbat-e-Deenar (SD) against CCl4 induced subchronic hepatic toxicity. In vivo study, albino rats were divided into 5 groups. Group I was control; Group II was experimental control treated with CCl4 (0.15 mL/kg, i.p. for 21 days); Groups III-IV treated with SD (2 mL/kg, p.o.) and MD (1,000 mg/kg, p.o.) for 5 days following CCl4 intoxication as in group 2 respectively; and Group V was positive control treated with silymarin (50 mg/kg, p.o.). In vitro hepatoprotective activity of SD and MD (25, 50, and 100 µg/mL) was assessed by SRB assay and flow cytometry analysis. CCl4 exposure significantly elevated the release of hepatic enzymes i.e. AST, ALT, LDH, and SALP in serum and lipid peroxidation in liver tissue which all these parameters were reversed after SD and MD administration. Therapy for 5 days also normalized the levels of antioxidant enzymes i.e. catalase, SOD, GPx, GR, tissue GSH, and aniline hydroxylase in CCl4 treated group. DNA damage and histological alterations caused by CCl4 were restored towards normal group. In vitro study showed protective effect of SD and MD against CCl4 treated HepG2 cell lines and rat hepatocytes. The results suggested that MD has a significant hepatoprotective potential and regulatory effect on oxidative stress than SD against CCl4 induced hepatotoxicity, and that this effect may be related to its antioxidant activity.

Protective efficacy of rutin against acrylamide-induced oxidative stress, biochemical alterations and histopathological lesions in rats.

Acrylamide is a well-known neurotoxicant and carcinogen. Apart from industrial exposure, acrylamide is also found in different food products. The present study deals with in vivo experiment to test the protective effect of rutin against acrylamide induced toxicity in rats. The study was carried out on female rats with exposure of acrylamide at the dose of 38.27 mg/kg body weight, orally for 10 days followed by the therapy of rutin (05, 10, 20 and 40 mg/kg orally), for three consecutive days. All animals were sacrificed after 24 h of last treatment and various biochemical parameters in blood and tissue were investigated. Histopathology of liver, kidney and brain was also done. On administration of acrylamide for 10 days, neurotoxicity was observed in terms of decreased acetylcholinesterase activity and oxidative stress was observed in terms of increased lipid peroxidation, declined level of reduced glutathione, antioxidant enzymes (superoxide dismutase and catalase) in liver, kidney and brain. Acrylamide exposure increased the activities of serum transaminases, lipid profile, bilirubin, urea, uric acid and creatinine in serum indicating damage. Our experimental results conclude that rutin showed remarkable protection against oxidative DNA damage induced by acrylamide, which may be due to its antioxidant potential.

Combined effect of N-acetyl cysteine, zinc, and selenium against chronic dimethylmercury-induced oxidative stress: a biochemical and histopathological approach.

Mercury (Hg), widely used in industry, is a great environmental health problem for humans and animals. Despite several reports regarding Hg toxicity, there is scarcity of data on its toxic manifestations on Sprague Dawley rats under realistic exposure conditions. Experimental studies have shown that sulphur-containing antioxidants have beneficial effects against the detrimental properties of Hg. The present work was aimed to study the therapeutic potential of combined administration of N-acetyl cysteine (NAC; 2 mmol/kg ip), zinc (Zn; 2 mmol/kg po), and selenium (Se; 0.5 mg/kg po) against dimethylmercury (DMM; 1 mg/kg po)-intoxicated male rats for 12 weeks. Exposure to DMM caused significant alterations in cytochrome P450 (CYP) activity, microsomal lipid peroxidation, and proteins. Activities of transaminases (aspartate aminotransferase/alanine aminotransferase), alkaline phosphatase, and lactate dehydrogenase in serum, as well as activities of CYP enzymes aniline hydroxylase (AH), amidopyrine-N-demethylase (AND) in liver microsomes and activities of acid phosphatase, alkaline phosphatase, glucose-6-phophatase, and succinic dehydrogenase in the liver and kidney, were significantly altered after DMM administration. DMM exposure also induced severe hepato-renal alterations at the histopathological level. NAC, along with Zn and Se, dramatically reversed the alterations in all of the variables more toward control. The study results conclude that protective intervention of combined treatment of NAC, along with Zn and Se, is beneficial in attenuating DMM-induced systemic toxicity.