INTRODUCTION:Arsenic trioxide is a highly effective chemotherapeutic agent that counteracts acute promyelocytic leukemia. However, the use of arsenic trioxide for managing acute promyelocytic leukemia has been associated with severe cardiotoxic effects. We investigated the cardioprotective effect of piperine in arsenic trioxide-induced cardiotoxicity in rats. METHODS:Cardiotoxicity was induced by administration of arsenic trioxide at 4 mg/kg body weight (bwt) orally for 30 days. The cardioprotective effect of piperine at 20 mg/kg orally was studied by cardiac biomarkers, oxidative parameters, and an electrocardiography study. RESULTS:Administration of arsenic trioxide at 4 mg/kg bwt orally for 30 days caused significant cardiovascular injury, confirmed by elevated cardiac enzymes CK-MB and LDH levels. Electrocardiographic (ECG) abnormalities were notable in the arsenic trioxide-treated group, such as prolonged QT and QTc intervals and reduced heart rate. There was significant myocardial oxidative impairment (TBARS increased, SOD and Catalase decreased) and inflammation (IL-6 increased). DISCUSSION:When piperine at 20 mg/kg was used, it decreased the CK-MB and LDH levels, reduced the prolonged QT and QTc intervals, and improved oxidative damage and inflammation. CONCLUSION:This study demonstrated that piperine at 20 mg/kg orally was protective in arsenic trioxide-induced cardiotoxicity in an experimental rat model. This study is the first to combine serum biomarkers and ECG analysis to demonstrate piperine's cardioprotective role. It may have clinical relevance in exploring the potential of piperine to reduce arsenic trioxide-induced cardiotoxicity.

BACKGROUND:To study the pharmacokinetic interaction of cephalosporin antibiotic ceftriaxone (CFT) with raw undiluted Ocimum sanctum L. leaf juice in chronic staphylococcal mastitis in caprine. MATERIALS AND METHODS:Chronic inflammation of the udder was evoked in goats by Staphylococcus aureus (J638) intracisternal inoculation 2000 cfu for 30 days into the left udder. Animals of Group I were given one single dose of CFT at 20 mg/kg i.v. Group II animals were given one single dose of CFT at 20 mg/kg i.v, and contemporary extracted fresh leaf juice of O. sanctum L. given at 5 ml/kg orally for 7 consecutive days. RESULTS:O. sanctum L. at 5 ml/kg oral had synergistic herb-drug pharmacokinetic interaction with CFT antibiotic (i.v.) and increased its bioavailability. It prolonged its rate of elimination (β) and enhanced the volume of distribution (Vdarea) and mean residence time in the body. Bioavailability and persistence of the antibiotic CFT and its metabolite ceftizoxime were increased in the milk from the udder. CONCLUSION:Administration of O. sanctum L. at 5 ml/kg oral with intravenous CFT at 20 mg/kg may be advocated for effective treatment of S. aureus inflammation of the udder in caprine.

Cadmium, a very hazardous metal, plays an ancillary part in free radicals' formation that harms the stomach tissues.Antioxidants like vitamin E and C, selenium, etc., can protect against the harmful effects of cadmium by averting the damage caused by reactive oxygen species (ROS).In this study, a novel technique was proposed for combating cadmium toxicity by combining nanoselenium with Phyllanthus niruri Hook.f. extract in rat model.The nanoselenium (SNP) and P. niruri fabricated selenium nanoparticle (PNFSNP) were characterised using fourier transform infrared (FTIR) and UV-Vis spectroscopic profiles.Total 48 wistar rats were equally divided into 8 experimental groups.Positive control rats were administered 40 mg/l of cadmium chloride for 28 days in drinking water and treatment groups were administered with 0.1 mg/kg selenium, 0.2 mg/kg nanoselenium and 0.2 mg/kg PNFSNP body weight orally, for 28 days, respectively.On 29 th day, the wistar rats were sacrificed, stomach was collected and examined histologically.Oral administration of CdCl 2 significantly induced haemorrhagic and necrotic lesions in gastric mucosa, degenerative alterations like epithelium discontinuity, mucin coat depletion, leucocytic infiltration, etc. Treatment with the selenium, SNP and PNFSNP significantly healed gastric damages.All treatments had protective effects against cadmium-induced oxidative damage; especially, PNFSNP has a promising therapeutic potential.Therefore, PNFSNP can be a forthcoming natural product for countering the cadmium chloride intoxication due to its potential gastroprotective effect that minimizes gastric toxicity effect of cadmium chloride.

Objective: To explore the cardioprotective effect of hesperidin against arsenic trioxide-induced cardiac toxicity in rats. Methods: Cardiac toxicity was induced by oral administration of 4 mg/kg arsenic trioxide for 30 days. Hematological, biochemical, electrocardiography, echocardiography, and histopathological examinations were performed. Results: Hesperidin decreased the neutrophil-to-lymphocyte ratio, calcium, creatine kinase-myoglobin binding, lactate dehydrogenase, IL-6, and lipid peroxidation, as well as increased sodium and potassium concentration and superoxide dismutase and catalase activity in arsenic trioxide-intoxicated rats. Moreover, it reduced peak systolic velocity and end-diastolic velocity while increasing heart rate. Arsenic trioxide-induced histopathological damage to cardiac tissue was prominently alleviated by hesperidin treatment. Conclusions: Hesperidin attenuates arsenic trioxide-induced cardiac toxicity in rats. Therefore, it can be further explored as a cardioprotective agent.

Cadmium is a metal that is frequently utilised in industry and released by fossil fuels. Free radical production by cadmium results in adverse effects damaging blood vessels, liver, heart and kidney. Morin is a secondary plant metabolite that acts as a free radical scavenger. This study looks into the effects of morin on cadmium-induced toxicity in developing chicken embryos by evaluating gross and histological changes. Forty-eight numbers of fertilised chicken eggs were divided into four groups, each containing twelve eggs. Eggs of group-I were taken as control, group-II were challenged with cadmium (3 mu g/egg), group-III were treated with cadmium (3 mu g/egg) and morin (5 mu g/egg), and group-IV were treated with cadmium (3 mu g/egg) and morin (10 mu g/egg) in ovo inoculation on day 1 of incubation. All of the eggs were incubated at 37 degrees C with a relative humidity of 65-75%. Six eggs from each group were carefully opened in a Petri dish on the 7th day to determine the degree of vascularization. The histology of the liver, heart, and kidney of chicken embryos was performed on the 14th day. Cadmium suppressed vascularization in 7th day chicken embryo. Enriching effect of morin was clearly visible with increased vascularization and arbourization of major and minor blood vessels. In 14th day chicken embryo, group-II showed severe necrosis, congestion, haemorrhage and moderate fibrosis in the hepatic, cardiac and renal tissues. The improved histology results justified that morin alleviated the tissue injuries. Thus, morin has the potency to minimize the cadmium-induced toxicity in chicken embryo.

Persistence of antibacterial drugs for prolonged period in milk increases the probability of antimicrobial resistance progress. Ceftizoxime was found to be excreted in milk for a prolonged period in goats, cows and buffaloes following intravenous injection of ceftriaxone and ceftizoxime. A single dose of ceftriaxone was administered intravenously in healthy control goats (group I) and a single oral dose of the commercial mammary protective polyherbal drug (1.9 gm) was given one hour prior to intravenous ceftriaxone injection in healthy (group II) and induced mastitic (group III) goats to evaluate milk disposition of ceftizoxime following single intravenous dosing of ceftriaxone at 42.25 mg kg−1.Ceftriaxone/ceftizoxime was analyzed by HPLC. The t1/2α and t1/2β values were 14.755 ± 2.733 and 149.079 ± 18.565 hour, respectively indicating prolonged persistence of ceftizoxime in milk. The polyherbal drug increased the milk concentration at later hours and hastened the excretion of ceftizoxime from milk compared to control group. Ceftriaxone could not be detected in milk. The study suggested that adjunct single or repeated therapy of the polyherbal drug may cause non persistence of ceftriaxone and shorter persistence of ceftizoxime in milk.

Bidyadhari river originates in Nadia district of West Bengal, India and then flows through North 24 Parganas district and now serves as a sewage and excess rainwater outlet from the city of Kolkata and adjacent area, which ultimately empties at the Bay of Bengal through the Indian Sundarban delta. Four different stations situated around the course of the river at considerable distances have been selected from the outfall of sewage canals at Kulti-Ghushighata (S1), where metropolitan sewages discharged and mixed up into water of Bidyadhari river, which ultimately carried through this river via stations Malancha (S2), Kanmari (S3) to Dhamakhali (S4), just before the river confluences with the larger Raimangal river at northern Sundarban delta. This study was conducted to estimate total mercury (Hg) concentration in waters (during high tides and ebb tides) and sediments of Bidyadhari river in pre-monsoon, monsoon and post-monsoon seasons during the period from March, 2012 to February, 2013 at those stations. It is revealed from the estimated data that agricultural runoff, sewage, effluents from various industries and Kolkata metropolitan, Salt Lake City and adjacent areas of North 24 Parganas district carried and discharged in Bidyadhari river through sewage canals are not so high in mercury content for sediment contamination but alarming in respect of water quality, which crosses the permissible limit of Hg for consumption (0.001 ppm) in wide range of areas at Kanmari and Dhamakhali around the estuary. Enhancement of Hg level in this river water and transportation of the metal through tidal effects to and fro mangrove land of Sundarban may be dangerous for aquatic lives and supposed to be grave concern for the ecology of the Sundarban delta including humans.

Objective: The objective was to study the effect of Bauhinia variegata L. stem bark powder as adjunct therapy in chronic Staphylococcus aureus mastitis in goat. Materials and Methods: Mastitis was induced by intracisternal inoculation of coagulase positive S. aureus (J638) at the concentration of 2000 colony forming units. Group I animals were treated with repeated dose of ceftriaxone at 20 mg/kg intravenously, and Group II animals were treated with once daily oral administration of B. variegata L. stem bark powder at 6 g/kg for 7 days followed by maintenance dose at 3 g/kg for next 7 days along with repeated dose of the antibiotic at 20 mg/kg intravenously at 4 days interval. Results: No significant improvement in the clinical condition of the udder was noticed in the group treated with repeated dose of ceftriaxone alone. However, in the group treated with B. variegata L. stem bark powder along with repeated dose of ceftriaxone, no S. aureus colony was seen at 96 h and onwards in milk samples with a marked decrease in somatic cell count and milk alkaline phosphatase activity and increased lactoperoxidase activity. Further, plasma and milk concentration of ceftriaxone/ceftizoxime was increased, which indicated antibacterial, bioenhancing and antiinflammatory properties of the bark powder. The Group II animals also exhibited marked reduction in polymorphonuclear cells and fibrous tissue indicating antifibrotic property of B. variegata L. Conclusion: B. variegata L. stem bark powder can be considered as an effective adjunct therapy to intravenous ceftriaxone in S. aureus chronic mastitis in goat.

This study has been conducted to estimate the concentration of total Cadmium (Cd) in different biotic and abiotic substrates including human in and around the Bidyadhari river of Sundarban delta. Bidyadhari river presently serves as a sewage and excess rainwater outlet from Kolkata metropolitan and adjacent area, which ultimately empties at the Bay of Bengal. The study reveals that the Cd content in surface water of the river and ponds as well as ground water was generally high up to 0.294 mu g/ml and 0.205 mu g/ml respectively during most of the seasons, which was above the maximum permissible level for drinking water as per various national and international standards like Indian Standard Specification, European Union, WHO, USEPA etc. Though, range of Cd in sediment of the river and ponds was 0.025 to 0.281 mu g/g and 0.018 to 0.317 mu g/g respectively but that was considerably higher in grasses up to 0.324 mu g/g. Backyard hen demonstrated considerably high levels of Cd in their egg up to 0.247 mu g/g in albumen and 0.272 mu g/g in yolk. Goat and cattle demonstrated Cd content in meat up to 0.295 mu g/g and milk up to 0.295 mu g/ml respectively which crosses the permissible levels recommended by different international standards. High Cd content in human hairs up to 1.11 mu g/g indicated considerably bioaccumulation of the metal in local inhabitants resides in the northern part of Sundarban mangrove eco-region. This whole observation may be considered as base line study to know the present status of Cd contamination and bioaccumulation in flora and fauna including humans in Sundarban mangrove eco-region to prepare mitigation planning against this carcinogen from the biota immediately.

Fifteen broiler chickens (COBB 400) of 42 days of age weighing 1.8 to 2.0 kg were equally divided into 3 groups, each consisting of 5 birds. Hepatopathy was induced by oral administration of paracetamol while nephropathy was induced by intravenous administration of uranyl nitrate. Kinetic study was investigated in healthy, hepatopathic and nephropathic birds following single oral administration of amoxicillin at 40 mg kg-1. Blood samples were collected at different time schedule. Plasma concentrations of amoxicillin in healthy, hepatopathic and nephropathic birds were 41.90 ± 5.59, 9.93 ± 0.76 and 38.75 ± 6.08 µg ml-1, respectively at 1 hr; 15.34 ± 1.99, 18.57 ± 1.66 and 67.40 ± 2.62 µg ml-1, respectively at 4 hr and 2.03 ± 0.28, 15.54 ± 0.82 and 30.63 ± 1.58 µg ml-1, respectively at 24 hr. Maximum plasma concentration was detected at 1 hr in healthy birds (41.90 ± 5.59 µg ml-1 ), at 8 hr in hepatopathic birds (23.51 ± 1.64 µg ml-1) and at 4 hr in nephropathic birds (67.40 ± 2.62 µg ml-1). The drug could not be detected in plasma beyond 24 hr in healthy, 72 hr in both hepatopathic and nephropathic birds. The concentration of amoxicillin was significantly (P < 0.01) higher in most of the samples of hepatopathic and nephropathic birds compared to healthy birds. Significant higher values (P < 0.01) of t1/2 K, AUC, and MRT and lower values of K and ClB in the hepatopathic and nephropathic birds in comparison to healthy birds were observed.

Severity of arsenic toxicity was reported to vary depending on its species. The present study reflects the status of different species of arsenic in goat following long-term exposure of arsenic leading to hepatic damage. The experiment was conducted with six black Bengal goats, which were administered with sodium arsenite orally at a dose rate of 2 mgkg(-1) daily for 84 days. Faeces, urine, hair and blood samples were collected from those animals at 14 days interval. Excretion of total arsenic was reduced from 56 days onwards through both faeces and urine indicating higher accumulation of arsenic in body. The speciation study revealed that urinary arsenic was mainly of organic type, whereas hair accumulated almost equal proportion of arsenite, arsenate and organo arsenicals. Goats excreted high proportion of organo arsenicals through faeces possibly due to hepatobiliary secretion of organo arsenic into the gut. Significantly elevated serum alanine aminotransferase and aspartate aminotransferase activities (p<0.05) along with histopathological changes in liver indicated hepatotoxicity. The arsenite fraction increased and organic proportion decreased in urine as the time progressed, which indicates that arsenite gets methylated in liver of goat. The study thus alluded that the toxicity of arsenic would aggravate if the animals were exposed for long time as the hepatotoxicity progressed resulting in decreased methylation and formation of organo arsenicals and decreased excretions through urine.

Abstract Background: The aim of the present study was to determine pharmacokinetic interaction of ceftriaxone and polyherbal drug (Fibrosin®) in lactating goats following single dose intramammary administration of ceftriaxone with 1 h pre-single dose oral administration of Fibrosin®. Methods: Pharmacokinetic interaction of ceftriaxone and Fibrosin® was evaluated in lactating goats following single dose intramammary administration of ceftriaxone at 50 mg/kg with 1 h pre-single dose oral administration of Fibrosin® (1.9 g). Estimation of ceftriaxone and its metabolite, ceftizoxime, was determined by high performance liquid chromatography. Results: Fibrosin® treated goats showed a typical absorption-reabsorption phase of ceftriaxone in plasma following intramammary administration. Neither ceftriaxone nor ceftizoxime was detected in the plasma and urine of goats without Fibrosin® treatment, however, ceftriaxone persisted for 36 h and ceftizoxime was present from 48 h to 72 h in the plasma of Fibrosin® treated goats. Ceftizoxime was also available from 72 h to 360 h post-dosing in milk in the presence of Fibrosin® following intramammary administration of ceftriaxone suggesting the polyherbal drug played a major role in the penetration of ceftriaxone from milk to systemic circulation. Furthermore, the polyherbal drug increased the bioavailability of ceftizoxime in milk following the metabolism of ceftriaxone. Conclusions: Polyherbal drug (Fibrosin®) plays a major role in the penetration of ceftriaxone from milk to systemic circulation and may be responsible for increased bioavailability of its metabolite in the mammary gland resulting in higher concentration and longer persistence of the drug in milk.