Screening of N-Benzoyl Isoserine Methyl Ester (N-bime) for anti-inflammatory analgesic activity and toxicity profile in animals

Background: Pain and inflammation are the basic processes involved in the pathogenesis of many diseases. Non-steroidal anti-inflammatory drugs are often used to treat rheumatic diseases. The study compound N-Benzoyl Isoserine Methyl Ester (N-bime) is a newly synthesized propionic acid derivative by National Chemical Laboratory, Pune. Since the biological data of this compound is not available, the present study has been planned to screen this compound for anti-inflammatory, analgesic activity and its toxicity profile in animals.Methods: Single dose toxicity study was carried out in rats. Anti-inflammatory activity was tested by Rat Hind Paw Oedema and Cotton Pellet Implantation method. For Analgesic activity, Acetic acid induced writhing and Tail Pinch method was used. Yeast induced Pyrexia was used for evaluation of anti-pyretic activity. Ibuprofen was the positive control. Data are presented as mean±SEM. Statistical analysis was performed by analysis of variance and students unpaired‘t’ test.Results: The test compound N-bime did not show any apparent adverse effects or mortality in the dose range 1mg - 500mg / 100gm body weight in animals. It showed better anti-inflammatory actions in higher doses as compared to Ibuprofen (p? 0.05). In acetic acid induced writhing test N-bime offered better protection against writhes, than Ibuprofen. But, both failed to demonstrate analgesic activity in the Tail Pinch method. N-bime showed a gradual decrease in temperature in the anti-pyretic test (P<0.001).Conclusions: The present study indicates that N-bime does possess anti-inflammatory, analgesic and weak anti-pyretic properties like the NSAIDs. It has proved to be safe in the dose range of 1mg - 500mg / 100gm body weight in rats and mice.

Gender differences in biochemical markers and oxidative stress of rats after 28 days oral exposure to a mixture used for weight loss containing p-synephrine, ephedrine, salicin, and caffeine

ABSTRACT The association of p-synephrine, ephedrine, salicin, and caffeine in dietary supplements and weight loss products is very common worldwide, even though ephedrine has been prohibited in many countries. The aim of this study was to evaluate a 28-day oral exposure toxicity profile of p-synephrine, ephedrine, salicin, and caffeine mixture (10:4:6:80 w/w respectively) in male and female Wistar rats. Body weight and signs of toxicity, morbidity, and mortality were observed daily. After 28 days, animals were euthanized and blood collected for hematological, biochemical, and oxidative stress evaluation. No clinical signs of toxicity, significant weight loss or deaths occurred, nor were there any significant alterations in hematological parameters. Biochemical and oxidative stress biomarkers showed lipid peroxidation, and hepatic and renal damage (p < 0.05; ANOVA/Bonferroni) in male rats (100 and 150 mg/kg) and a reduction (p < 0.05; ANOVA/Bonferroni) in glutathione (GSH) levels in all male groups. Female groups displayed no indications of oxidative stress or biochemical alterations. The different toxicity profile displayed by male and female rats suggests a hormonal influence on mixture effects. Results demonstrated that the tested mixture can alter oxidative status and promote renal and hepatic damages.

RESUMO A associação de p-sinefrina, efedrina, salicina, e cafeína em suplementos alimentares e produtos para perda de peso é muito utilizada em todo o mundo, embora a efedrina tenha sido proibida em muitos países. O objetivo deste estudo foi avaliar o perfil de toxicidade à exposição oral de 28 dias à associação de p-sinefrina, efedrina, salicina e cafeína (na proporção de 10:4:6:80 m/m respectivamente) em ratos Wistar machos e fêmeas. Diariamente, os animais foram observados quanto ao peso corporal, sinais de toxicidade, morbidade e mortalidade. Após 28 dias, os animais foram sacrificados e o sangue coletado para avaliações hematológicas, bioquímicas e de estresse oxidativo. Não se observaram sinais clínicos de toxicidade, tampouco perda significativa de peso, mortes, ou quaisquer alterações significativas nos parâmetros hematológicos. Biomarcadores do estresse oxidativo e bioquímicos mostraram peroxidação lipídica, danos renais e hepáticos (p < 0,05; ANOVA/Bonferroni) em ratos machos (100 e 150 mg/kg) e a redução (p < 0,05; ANOVA/Bonferroni) nos níveis de glutationa reduzida (GSH) em todos os grupos de machos tratados. Nas fêmeas, não houve indícios de estresse oxidativo, nem alterações bioquímicas. O diferente perfil de toxicidade entre os gêneros sugere influência hormonal nos efeitos de mistura administrada. A associação testada pode alterar o estado oxidativo e promover danos renais e hepáticos.

Moringa oleifera impairs the morphology and functions of the kidney in adult Wistar rats / Moringa oleifera altera la morfología y funciones del riñón en ratas Wistar adultas

We tested the hypothesis that Moringa oleifera impairs the morphology and functions of the kidney in rats. Twenty-four adult male Wistar rats were employed in the study. Rats of Control Group I received physiological saline while rats of Groups II ­ IV received 250, 500 and 750 mg/kg bodyweight of methanolic extract of Moringa oleifera respectively for twenty one days. No behavioral anomalies were observed in rats of Groups I ­ IV. Rats of Control Group I gained statistically significant increased bodyweight while rats of Groups II ­ IV experienced non-significant decreased bodyweight during experimental procedure. (P0.05). No statistical significant differences (P0.05) were observed in the analyses of the relative weights of kidneys of rats of Groups I ­ IV. Histological examinations showed normal cyto-architecture of the kidneys of rats of Group I while the Capsular spaces of the kidneys of rats of Groups II ­ IV appeared wider than those of Group I. Statistical analyses showed significant higher levels (P0.05) of Alanine and Aspartate Transaminases, and serum urea in rats of Groups II ­ IV in a non- dose-dependent manner when compared to rats of Group I. Our findings are consistent with the stated hypothesis.

Se puso a prueba la hipótesis que Moringa oleifera altera la morfología y función del riñón en ratas. Fueron utilizadas 24 ratas Wistar macho adultas. El grupo control recibió suero fisiológico mientras que los Grupos II a IV recibieron 250, 500 y 750 mg/kg peso corporal del extracto metanólico de Moringa oleifera respectivamente, durante 21 días. No se observaron anomalías en el comportamiento en ratas de los Grupos I - IV. En las ratas del grupo de control se registró un aumento de peso corporal estadísticamente significativo, mientras que las ratas de los grupos II - IV experimentaron una disminución no significativa de peso corporal durante el procedimiento experimental (P0,05). No se observaron diferencias estadísticamente significativas (P0,05) en el análisis de los pesos relativos en riñones de las ratas de los grupos I - IV. Los exámenes histológicos mostraron citoarquitectura normal de los riñones de las ratas del grupo I, mientras que en ratas de los grupos II ­ IV los espacios capsulares de los riñones aparecían más amplios que los del Grupo I. Los análisis estadísticos mostraron niveles superiores significativos ( P 0,05 ) de la alanina y aspartato aminotransferasa, y de urea en suero en ratas de los Grupos II - IV no dependiente de la dosis, en comparación con las ratas del Grupo I. Estos resultados coinciden con la hipótesis planteada.

A supplementary report on the toxic manifestations of CHOP regimen in subjects with intermediate grade NHL.

Cancer chemotherapy engenders a gamut of unpredictable and perilous toxicities, which can cause substantial mortality, morbidity, and results in escalated healthcare costs due to increased requirement for ameliorative treat-ments and toxicity-related hospitalization. The main objective of this article is to report a range of adverse effects of CHOP regimen in patients with intermediate grade Non-Hodgkin’s Lymphoma (NHL). This randomized prospective study was conducted on de novo intermediate grade NHL patients, aged >20≤60 years, receiving CHOP chemotherapy regimen. Out of 30 patients who satisfied the inclusion criteria, only 25 patients completed 6 cycles of chemotherapy and were evaluated for various toxicities. Evaluation of all the 25 subjects showed that, in comparison with the baseline, most patients exhibited toxic damages. The hepatopancreatic, dermatological, vascular and nephrological damages, eventually resulted in weight loss, hepatomegaly, alopecia, hypotension, as well as abnormal levels of serum liver markers, serum creatinine and blood glucose. But, the necessity to interrupt the CHOP treatment did not arise in any of the patients. Thus, in this study combination chemotherapy with CHOP protocol was well tolerated by majority of the subjects.

A supplementary report on the toxic manifestations of CHOP regimen in subjects with intermediate grade NHL.

Cancer chemotherapy engenders a gamut of unpredictable and perilous toxicities, which can cause substantial mortality, morbidity, and results in escalated healthcare costs due to increased requirement for ameliorative treat-ments and toxicity-related hospitalization. The main objective of this article is to report a range of adverse effects of CHOP regimen in patients with intermediate grade Non-Hodgkin’s Lymphoma (NHL). This randomized prospective study was conducted on de novo intermediate grade NHL patients, aged >20≤60 years, receiving CHOP chemotherapy regimen. Out of 30 patients who satisfied the inclusion criteria, only 25 patients completed 6 cycles of chemotherapy and were evaluated for various toxicities. Evaluation of all the 25 subjects showed that, in comparison with the baseline, most patients exhibited toxic damages. The hepatopancreatic, dermatological, vascular and nephrological damages, eventually resulted in weight loss, hepatomegaly, alopecia, hypotension, as well as abnormal levels of serum liver markers, serum creatinine and blood glucose. But, the necessity to interrupt the CHOP treatment did not arise in any of the patients. Thus, in this study combination chemotherapy with CHOP protocol was well tolerated by majority of the subjects.