The present study was designed to determine the lethal dose 50 (LD ₅₀ ) of combination of cypermethrin, a pyrethroid, and endosulfan, an organochlorine compound in Wistar rats. LD ₅₀ is the amount (dose) of a chemical, calculated as per the concentration of chemicals that produces death in 50% of a population of test animals to which it is administered by any of a variety of methods. A single oral dose of combination of cypermethrin and endosulfan were dissolved in dimethyl sulfoxide (DMSO) in a ratio of 1:1 and administered orally at the concentration of 165 mg/kg body weight (b.w), 330 mg/kg b.w, 660 mg/kg b.w, and 1320 mg/kg b.w to experimental animals. LD ₅₀ was calculated according to the method described by Miller and Tainter (1994) and was observed as 691.83 mg/kg b.w for this combination. Single dose of test article at 165 mg/kg b.w did not reveal any toxic signs or behavioral alterations, hence considered as No observed Adverse Effect level (NOAEL).

The study investigated the immunotoxic and genotoxic effect of arsenic and its different species on goats. It was found that arsenic causes haematological crisis. Histopathological changes in spleen and reduced serum immunoglobulin G level without any changes in formazan production in arsenic-treated animals indicated that arsenic is toxic to the humoral immune system. Increased caspase-3 production and higher number of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling)-positive bone marrow cells along with oligonucleosomal DNA fragmentation on agarose gel suggested apoptosis induction by arsenic in the bone marrow cells of goat. Total arsenic concentration in the plasma, bone marrow, and spleen of the exposed group was, respectively, 1.22 ± 0.11, 2.20 ± 0.21, and 3.39 ± 0.14 ppm. Speciation study revealed that arsenite and organoarsenic were the major arsenic species in these samples, suggesting their role in immunotoxic and genotoxic potential in goats.

Introduction: Wellbutrin (bupropion hydrochloride; WB), an anti-depressant of the aminoketone class is new highly selective norepinephrine and dopamine reuptake inhibitor; it is effective in the treatment of patients with major depression. Materials and Methods: To investigate the in vitro effects of WB in human cultured peripheral blood lymphocytes and human cortical neural (HCN2) cell lines, micronucleus, sister chromatid exchange analysis, cellular viability, and comet assays were employed. The present study is to our knowledge, the first report on WB genotoxicity in cultured human peripheral blood lymphocytes and its cytotoxicity in the HCN2 cell line. We have also investigated the genotoxic potential of WB to induce chromosomal aberrations. Results: WB-induced cytotoxicity (measured as reduction of the nuclear division index) possibly prevented the division of damaged cells. Conclusion: We conclude that although, WB exerts potential genotoxic effects in cultured lymphocytes, its cytogenetic effects are very unlikely to occur in blood cultures of WB-administered subjects.

Background: Non-ionizing radiofrequency radiation has been increasingly used in industry, commerce, medicine and especially in mobile phone technology and has become a matter of serious concern in present time. Objective: The present study was designed to investigate the possible deoxyribonucleic acid (DNA) damaging effects of low-level microwave radiation in brain of Fischer rats. Materials and Methods: Experiments were performed on male Fischer rats exposed to microwave radiation for 30 days at three different frequencies: 900, 1800 and 2450 MHz. Animals were divided into 4 groups: Group I (Sham exposed): Animals not exposed to microwave radiation but kept under same conditions as that of other groups, Group II: Animals exposed to microwave radiation at frequency 900 MHz at specific absorption rate (SAR) 5.953 × 10^–4 W/kg, Group III: Animals exposed to 1800 MHz at SAR 5.835 × 10^–4 W/kg and Group IV: Animals exposed to 2450 MHz at SAR 6.672 × 10^–4 W/kg. At the end of the exposure period animals were sacrificed immediately and DNA damage in brain tissue was assessed using alkaline comet assay. Results: In the present study, we demonstrated DNA damaging effects of low level microwave radiation in brain. Conclusion: We concluded that low SAR microwave radiation exposure at these frequencies may induce DNA strand breaks in brain tissue.

Mycotoxins are fungal toxin and contaminated to human through food-stuffs. Hematological abnormality, mainly thrombocytopenia and leukopenia are induced after consumption of mycotoxin. Experiments were conducted to evaluate the hematotoxicity of trichothecenes mycotoxins in Sprague-Dawley rats. Hematological parameters viz. Hemoglobin, hematocrit, erythrocyte count (RBC), white blood cell count (WBC), lymphocytes, monocytes, neutrophils, eosinophils, basophils, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cell distribution width, mean platelet volume, plateletcrit and platelet distribution width were determined at 0, 6, 12 and 24 h after injection of 0.5 ml of T-2, Deoxynivalenol (DON), nivalenol, zearalenone, neosolaniol, ochratoxin-B mycotoxin equivalent to 1 × 10^­-3 μg/μl to Sprague-Dawley rats. Experiments showed that trichothecenes toxin produces severe hematological alternation. The reductions of RBC and WBC were observed in all Fusarium mycotoxins treated group. T-2 toxin group shows severe toxicity as compared to other mycotoxin treated group. DON is the least hematotoxicity and T-2 the most.

This study conducted on 423 inhabitant (372 adults and 51 children) blood samples were collected from patients hosted in the Emergency Hospital of Mansoura University. The clinical diagnosis of such patients was acute insecticides poisoning. The aim of the present study is to study patients with cholinesterase (ChE) inhibitor organophosphorus insecticides intoxication from the laboratory point of view. The plasma samples were analyzed for levels of ChE enzyme and acetyl cholinesterase enzyme activity by spectrophotometer. The pesticides were identified using Gas Chromatography-Electron Captured Detector (GC-ECD). The results of GC-ECD instrument of all patients revealed that parathion (organophosphorous insecticide) poisoning was found in their blood samples. The mode of poisoning was accidentally by inhalation and skin contact. The poisoning cases of children were of mild poisoning. The degrees of poisoning of adults were severe in 138, moderate in 201 and mild in 33 cases. In conclusion, results of the present study revealed that the widely used insecticides in Dakahlyia governorate are the organophosphorous insecticides specifically parathion insecticide.

Background: In the present study, cigarette smoke contains more than four thousand chemicals, many of which are known to be carcinogen or cancer promoter. Many epidemiological reports suggest that cigarette smokers are at a greater risk of other cancers such as oropharynx, stomach, pancreas, liver, kidney, urinary bladder, colon, and breast, however, the few epidemiological reports are available on the role of cigarette smoke in the development of prostate cancer. In this study, we investigated the effects of farnesol against cigarette smoke extract (CSE)-induced oxidative stress in prostate. Materials and Methods: Farnesol was administered by gavage (50 mg/kg and 100 mg/kg b.wt. in corn oil) one time daily for 7 days. On day 7, rats were exposed to cigarette smoke via intratracheal instillation of aqueous CSE. CSE enhanced prostatic xanthine oxidase activity and lipid peroxidation (LPO) along with decrease in prostatic glutathione content, antioxidant enzymes activities, viz., glutathione peroxidase, glutathione reductase, and catalase. Results: Pre-treatment of rats with farnesol (50 mg/kg and 100 mg/kg b.wt. orally) resulted in significant decreased in xanthine oxidase activity and LPO at both the doses. The level of reduced glutathione, the activities of glutathione dependent enzymes and antioxidant enzymes were also augmented to significant level with pre-treatment with farnesol. Conclusion: Thus, our data suggests that farnesol is a potent defense against CSE induced prostatic oxidative damage in rodent model of experiment.

Background: Cisplatin (CP) is an effective drug in cancer therapy to treat the solid tumors, but it is accompanied with nephrotoxicity. The protective effect of estrogen in cardiovascular diseases is well-documented; but its nephron-protective effect against CP-induced nephrotoxicity is not completely understood. Materials and Methods: Thirty ovarectomized Wistar rats were divided in to five groups. Groups 1-3 received different doses of estradiol valerate (0.5, 2.5 and 10 mg/kg/week) in sesame oil for 4 weeks, and at the end of week 3, a single dose of CP (7 mg/kg, intraperitoneal [IP]) was administrated. Group 4 (positive control) received the same regimen as group 1-3 without estradiol without vehicle. The negative control group (Group 5) received sesame oil during the study. The animals were sacrificed 1 week after CP injection for histopathological studies. Results: The serum level of blood urea nitrogen and creatinine, kidney tissue damage score (KTDS), kidney weight and percentage of body weight change in CP-treated groups significantly increased (P < 0.05), however, there were no significant differences detected between the estrogen-treated groups (Groups 1-3) and the positive control group (Group 4). Although, estradiol administration enhanced the serum level of nitrite, it was not affected by CP. Finally, significant correlation between KTDS and kidney weight was detected (r² = 0.63, P < 0.01). Conclusion: Estrogen is not nephron-protective against CP-induced nephrotoxicity. Moreover, it seems that the mechanism may be related to estrogen-induced oxidative stress in the kidney, which may promote the nephrotoxicity.

The restorative potential of trans-resveratrol (RV) was investigated in a rat neuronal cell line (PC12) exposed to organophosphate pesticide-monocrotophos (MCP). RV shows significant protection against MCP-induced alterations in PC12 cells by restoration of oxidative stress-mediated apoptosis and cytotoxicity. RV treatment significantly reduced reactive oxygen species (ROS) production and lipid peroxidation, and also restored glutathione levels and mitochondrial membrane potential, in cells receiving MCP. Restoration of markers such as cytochrome c, Bax, Bcl-2 and caspase-3 also confirms the effectiveness of RV against MCP-induced, mitochondria-mediated apoptosis in PC12 cells. The data identify the protective/restorative potential of RV against MCP-induced neuronal damages by affecting ROS production and the level of antioxidant defence enzymes.

Cisplatin was administered at the dose rate of 30 mg m^-2 daily intravenously consecutive for 7 days in goats. Blood samples (2 ml) were collected from each goat at '0' hr and then at weekly interval and centrifuged immediately at 3000 rpm for 20 min to separate plasma, which were used for estimation of blood urea nitrogen (BUN), plasma creatinine (CRT), gamma glutamyltransferase (gGT), and glomerular filtration rate (GFR). Total volume of urine of each goat was recorded, and 5 ml of urine samples were collected for estimation of GFR. Blood urea nitrogen started to increase significantly from 7 days post-dosing and achieved a peak on day 14. Higher values persisted up to 91 days. Plasma creatinine level was significantly higher in all samples on day 7 onwards, and it was maintained up to day 91 post-dosing compared to control samples ('0' day) whilst GFR declined significantly from day 7 and attained a minimum values on day 70. GFR was almost <60% up to 91 days. The signs like emaciation, loss of body weight, and oliguria were observed. The values of all 4 biomarkers showed a chronic renal failure in goats.

Background: Endosulfan, a neurotoxic organochlorine insecticide and cypermethrin, a synthetic pyrethroid insecticide used to control pests in domestic, industrial, and agricultural situations. Materials and Methods: The present study was carried out to investigate the acute oral toxicity, behavioral and histopathological changes of combination of endosulfan and cypermethrin in albino rats. According to Miller and Tainter analysis method, at 48 h, LD50 value of combination of endosulfan and cypermethrin (ratio 1:1) in rats was found to be 691.83 mg/kg bw by oral gavage. Results: When combination of both these pesticides was administered orally at concentration of 103.72 mg/kg bw, 172.95 mg/kg bw and 207.50 mg/kg bw, respectively, as a single dose, no significant changes in behavior of rats was observed, neither in dosed nor in control group of rats. Combination of endosulfan- and cypermethrin-treated rats showed mild histopathological changes in liver and kidney in group IV (207.50 mg/kg BW) as compared to the control. However, no significant changes were observed in brain and small intestine at either dose of combination of endosulfan and cypermethrin with respect to control. Conclusion: Thus, the present study, first of its kind in India, demonstrated the oral toxicity, behavioral, and histo-architectual alterations after induction of combination of endosulfan and cypermethrin at acute doses in Wistar rats.

Recently, sodium valproate (VPA) has been proven as histone deacetylase (HDAC) inhibitor and potentiates the cytotoxicity of anticancer drugs, and also exhibit promising anti-cancer activity. Present study aimed to investigate the influence of pre- and post-treatment of VPA on cyclophosphamide (CP) induced genotoxicity and germ cell toxicity in mice. All the animals were treated with VPA at the dose of 500 mg/kg/day on alternate day thrice/week for a period of two weeks, CP at the dose of 200 mg/kg on 7 ^th and 15 ^th day and sacrificed 24 h after administration (i.p.) of the last dose. End point of evaluation includes sperm count, sperm head morphology, sperm comet assay and histology. VPA treatment significantly decreases CP induced sperm count, testes and epididymis weight; increased sperm head abnormality and sperm DNA damage. Both VPA pre- and post-treatment augmented CP induced DNA damage and the germ cell toxicity; however, pre-treatment induced more cytotoxicity and genotoxicity as compared to post-treatment.

Objectives: TLPL/AY/03/2008 is a polyherbal formulation intended for treatment of osteoarthritis, rheumatoid arthritis, lumbago, spondylitis etc., Acute and repeated dose 90-days studies were conducted to evaluate the safety profile of TLPL/AY/03/2008 in rats. Materials and Methods: In acute study, TLPL/AY/03/2008 was orally administered to Sprague Dawley rats at 2000 mg/kg. In repeated dose study, TLPL/AY/03/2008 was administered to rats at 200, 500 and 1000 mg/kg through oral gavage for 90 days and assessed for treatment related changes in body weight, feed consumption, hematological, biochemical and pathological parameters. Histopathological examination was conducted for tissues from control and the high dose groups and was extended to target organs from the lower dose and recovery groups. Results: In acute study, the test item did not produce any mortality or adverse clinical signs. In the 90-days oral toxicity study, animals did not exhibit any toxicity symptoms and no deaths were observed. No significant changes were found in hematological and biochemical endpoints. Also, toxicologically significant alterations in relative organ weights were not observed. Microscopic findings of mild to marked, diffuse hepatocellular degeneration (vacuolar changes with granular of cytoplasm and pyknotic nuclei of hepatocytes) was noticed in males at 1000 mg/kg body weight. Animals of recovery group (1000 mg/kg) did not show any changes when compared with control group animals indicating the complete reversal. Conclusions: Based on the findings of the study, the median lethal dose of TLPL/AY/03/2008 was found to be more than 2000 mg/kg. The No Observed Adverse Effect Level (NOAEL) of TLPL/AY/03/2008 can be considered as 1000 mg/kg in both male and female rats, under the experimental conditions and doses employed.

Objective: The present study was undertaken to determine target organ safety of "Immuforte" to establish relationship between dose or exposure and response and also to identify potential parameters for monitoring adverse effects of "Immuforte" in clinical studies, if any. Materials and Methods: A total of 40 males and 40 females were randomly assigned to the four groups, namely group I (vehicle control; gum acacia), group II (120 mg/kg BW of Immuforte in gum acacia), group III (360 mg/kg BW of Immuforte in gum acacia), and group IV (600 mg/kg BW of Immuforte in gum acacia) consisting of 10 males and 10 females in each group. Additionally, a recovery group (600 mg/kg BW of Immuforte in gum acacia) containing 5 males and 5 females was included. Results: The results showed significant decrease in percent lymphocyte count of high and mid dose groups as compared to control group. The percent neutrophil counts in all the three treated groups of male and female rats were found to be significantly higher than that of control group ( P < 0.05). In females MCV values in low dose and mid dose were significantly higher as compared to control ( P < 0.05). The males from low dose group showed significant decrease in total serum protein, globulin, electrolytes, direct bilirubin, creatinine levels, whereas in mid dose group along with albumin, globulin. A significant decrease in AST and cholesterol was observed. In females, significant decrease was observed in total protein and globulin of low dose and mid dose of Immuforte-treated rats ( P < 0.05). Though few hematological and biochemical parameters were different from control group, no does related response was observed and further, all these values were comparable with historical control data of the colony. Terminal body weight, organ weight, gross, and histopathology did not reveal any toxicity-related any adverse effects. Heavy metal analysis of the blood samples collected from terminally sacrificed animals did not show presence of heavy metals viz. lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As). Conclusion: The results of the present study demonstrated that Immuforte does not cause any observable toxicity at doses used in the study when administered for the period of 90 days and is safe for the human use and thus, Immuforte could be used safely for therapeutic use in humans.

Battery manufacturing workers are occupationally exposed to lead (Pb), which is a highly toxic heavy metal. The aim of this study was to investigate the blood lead levels (BLL) of 30 battery manufacturing workers and find the correlation between BLL, micronucleated cell (MNC) frequency, binucleated cell (BNC) frequency in buccal mucosal cells and malondialdehyde concentrations in serum. 30 subjects of the BMW group, exposed to lead, and 30 control subjects, matched with the exposed subjects with respect to age, socio-economic status, sex, diet, smoking and drinking habits, were monitored for this study. BLL was found to have highly significant difference between both the groups ( P < 0.001). The serum MDA levels were observed at significantly higher levels (6.76 ± 3.26) for the exposed group as compared to the control group (2.10 ± 1.02; P < 0.001). Buccal micronucleus test showed that both MNC and BNC frequencies were higher among the workers, in comparison to the control subjects. A positive correlation has been found between BLL and all the parameters. Our results indicate an increased health associated risk for workers occupationally exposed to lead.

Aims: This study is an attempt to evaluate the tissue protective efficacy of isolated flavonoid and hydro-ethanolic extract of Euphorbia neriifolia (HEEN) leaves against N-nitrosodiethylamine (DENA) induced renal carcinoma. Materials and Methods: Carcinogenicity was induced in Albino mice by oral administration of DENA (50 mg/kg body weight). The HEEN (150 and 400 mg/kg body weight), Butylated hydroxyanisole (BHA; 0.5 and 1%), and Euphorbia neriifolia flavonoid (ENF; 50 mg/kg body weight) were evaluated for their possible tissue carcinogenesis protective potential. Results: DENA treated animals showed alterations in normal renal histo-architecture, which comprised of necrosis (N) and vacuolization of the cells. On the other hand, the mice treated with Euphorbia neriifolia lower (ENL) and higher (ENH) dose and ENF before intoxicated with DENA showed that the renal cells were normal (Day 31). Whereas, BHA higher (BHAH) and lower (BHAL) dose failed to diminish the abnormalities caused by DENA. Conclusions: The findings of the present study Suggested that ENH and ENF showed highest renal-protective activity among all the pretreatments. The results could also be expressed in the order of ENH > ENF > ENL > BHAH > BHAL.

Cadmium (Cd) is currently of great concern in rapidly industrializing countries-India, China. Their products consumed especially due to increase demand in many developing countries like Nigeria can result in adverse effects. Cd is a ubiquitous environmental pollutant and toxicant and humans are continually exposed to the toxic effects of Cd primarily through food as well as from environmental pollution through industrial activities. Maternal exposure to Cd has been associated with the delivery of low-birth weight babies and an increase incidence of spontaneous abortion. Cd a toxic metal can displace zinc (Zn) an essential element necessary for normal fetal development and growth. With this consideration, 160 subjects comprising of 125 pregnant and 35 non-pregnant subjects as controls were recruited for this study. The pregnant subjects were classified according to the three trimesters of pregnancy as followed; 35, 35, and 55 from the first to the third trimesters respectively. The third trimester subjects were followed-up until after delivery where neonatal parameters (birth weight, head circumference, and length) of babies were measured. 32 (58%) of the women delivered babies with normal birth weight, 19 women (35%) delivered babies with low-birth weight while four women (7%) delivered babies with high- birth weight. Subject who delivered low-birth weight babies had significantly higher Cd concentration and lower Zn concentration and body mass index when compared with those with normal weight babies. These results suggest that Cd indeed has some toxic effects on neonatal birth weight.

Mushrooms are commercially cultivated over the world and safe for human consumption, except in those with known allergies. Among the thousands of mushroom species identified, few are considered to be edible. Mushroom hunting has emerged as an adventure and recreational activity in recent decades. Wild forms of mushrooms are often poisonous and visually mimic the edible ones, thus leading to mistaken harvesting, consumption, and toxicities. In literature, various systemic toxic syndromes associated with mushroom poisoning have been described. We report four members of a family with muscarinic manifestations after accidental consumption of poisonous mushrooms. The Clitocybe species of mushrooms they consumed resulted in their muscarinic toxicity. Patients with muscarinic mushroom toxicity have early onset of symptoms and they respond well to atropine and symptomatic supportive care.