Sujata Maiti Choudhury

Antineoplastic activities of MT81 and its structural analogue in Ehrlich ascites carcinoma-bearing Swiss Albino mice.

Many fungal toxins exhibit in vitro and in vivo antineoplastic effects on various cancer cell types. Luteoskyrin, a hydroxyanthraquinone has been proved to be a potent inhibitor against Ehrlich ascites tumor cells. The comparative antitumor activity and antioxidant status of MT81 and its structural analogue [Acetic acid-MT81 (Aa-MT81)] having polyhydroxyanthraquinone structure were assessed against Ehrlich ascites carcinoma (EAC ) tumor in mice. The in vitro cytotoxicity was measured by the viability of EAC cells after direct treatment of the said compounds. In in vivo study, MT81 and its structural analogue were administered (i.p.) at the two different doses (5, 7 mg MT81; 8.93, 11.48 mg Aa-MT81/kg body weight) for 7 days after 24 hrs. of tumor inoculation. The activities were assessed using mean survival time (MST), increased life span (ILS), tumor volume, viable tumor cell count, peritoneal cell count, protein percentage and hematological parameters. Antioxidant status was determined by malondialdehyde (MDA) and reduced glutathione (GSH ) content, and by the activity of superoxide dismutase (SOD) and catalase (CA T). MT81 and its structural analogues increased the mean survival time, normal peritoneal cell count. They decreased the tumor volume, viable tumor cell count, hemoglobin percentage and packed cell volume. Differential counts of WBC, total counts of RBC & WBC that altered by EAC inoculation, were restored in a dose-dependent manner. Increased MDA and decreased GSH content and reduced activity of SOD, and catalase in EAC bearing mice were returned towards normal after the treatment of MT81 and its structural analogue. Being less toxic than parent toxin MT81, the structural analogue showed more prominent antineoplastic activities against EAC cells compared to MT81. At the same time, both compounds exhibit to some extent antioxidant potential for the EAC-bearing mice.

Toxicological potential of mycotoxin MT81 and its benzoylated derivative on testicular spermatogenesis and steroidogenesis in mature male Wistar albino rats

Mycotoxin MT81 was isolated, purified, and identified from a fungal strain of Penicillium nigricans. It is a CNS depressant, hyperglycemic agent and produces massive bone marrow depression, hepatotoxicity, and nephrotoxicity. Its benzolylated analog (benzoylated-MT81) was synthesized in our laboratory having a LD50 value of 87.1 mg/kg body weight in mice. This study was designed to assess the toxicological effects of mycotoxin MT81 and its analog on testicular spermatogenesis and steroidogenesis in mature albino rats. The sperm count and percentage of motile sperm were decreased markedly in MT81- and benzoylated-MT81-treated rats. The body weight and the weight of testis were reduced, whereas weight of adrenal gland was increased in a dose-dependent manner in the toxin-treated rats. MT81 and its derivative caused accumulation of ascorbic acid and total cholesterol in the testis and reduction in the activities of Δ5-3β-hydroxysteroid dehydrogenase (Δ5-3β-HSD) and glucose-6-phosphate dehydrogenase (G-6-P-D), whereas the ascorbic acid and cholesterol content of adrenal gland were decreased and enzyme activities were elevated. This experiment suggests that MT81 and benzoylated-MT81 both produce inhibition of testicular spermatogenesis and steroidogenesis but increase adrenal steroidogenesis and ultimately sterility of male rats.

Synthesis and characterization of biogenic metal nanoparticles and its cytotoxicity and anti-neoplasticity through the induction of oxidative stress, mitochondrial dysfunction and apoptosis

In the present study, we demonstrate a simple, cost-effective and eco-friendly method for biogenic synthesis of silver nanoparticles (AgNPCGs) using ethanolic extract of Calotropis gigantea latex. Attempts were made to characterize these biogenic silver nanoparticles AgNPCGs and also to test its cytotoxic, anti-neoplastic and apoptotic potential through the induction of oxidative stress, mitochondrial dysfunction. AgNPCGs were characterized by UV-vis spectroscopy, dynamic light scattering (DLS) and surface zeta potential measurement, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM) and selected area electron diffraction, scanning electron microscopy (SEM), energy-dispersive X-ray fluorescence spectrometry (EDX). UV visible spectroscopy showed an intense surface plasmon resonance band at 431nm which clearly reflected the formation of silver nanoparticles. FTIR study revealed that latex extract acted as reducing and stabilizing agent for the synthesis of AgNPCGs. Energy dispersive X-ray spectroscopy confirmed the presence of silver as a major component of synthesized AgNPCGs. SEM and TEM studies showed that the synthesized AgNPCGs were nearly spherical in shape with an average size of 2.338nm. The selected area electron diffraction pattern and XRD studies confirmed the crystalline nature of AgNPCGs. AgNPCGs exhibited in-vitro cytotoxic activity against Ehrlichs ascites carcinoma (EAC), Jurkat and MCF-7 cells at respective IC50 doses without producing cytotoxicity to mice and human lymphocytes. Significant chromatin condensation, DNA fragmentation, cell cycle arrest at G2/M phase, up-regulation of Bax and caspase-3 and down-regulation of Bcl-2 were observed in AgNPCGs treated EAC cells. The results suggest that biogenic silver nanoparticles AgNPCGs could be a potential chemotherapeutic formulation for cancer therapy.

Lipid peroxidative damage, alterations in antioxidant status and morphological changes in rat erythrocytes on lambda-cyhalothrin exposure and its attenuation by taurine

Lambda-cyhalothrin, a third generation type II pyrethroid, is used predominantly in agriculture production and animal husbandry. A study was conducted to investigate lambda-cyhalothrin induced oxidative streßs, morphological changes of erythrocytes and other hematological biomarkers in rat and its amelioration by taurine, 2-amino ethane-sulfonic acid, a ß-amino acid. Rats were randomly divided into six groups and lambda-cyhalothrin was orally administered at two dose levels (10.83 and 15.17 mg/kg body wt), singly or combined with pretreated taurine (50 mg/kg body wt) for consecutive 14 days. Treatment of Lambda-cyhalothrin resulted in an increase in malondialdehyde, oxidized glutathione level and depletion of reduced glutathione level, superoxide dismutase, catalase, glutathione-s-transferase and glutathione peroxidase in erythrocyte compared to control. Scanning electron microscopic studies showed a marked alteration in the morphology of Lambda-cyhalothrin treated erythrocytes. Lambdacyhalothrin exposure also showed a significant decrease in erythrocyte count, hemoglobin percentage, haematocrit and red cell indices, whereas a significant increase in white blood cells and lymphocyte count was observed. However, pretreatment with taurine significantly restored the above said parameters. These findings revealed that lambda-cyhalothrin exposure produced oxidative stress, morphological changes of erythrocytes and other hematological biomarkers and its amelioration was accomplished by taurine through its reactive oxygen species scavenging activity.

Lambda Cyhalothrin Elicited Dose Response Toxicity on Haematological, Hepatic, Gonadal and Lipid Metabolic Biomarkers in Rat and Possible Modulatory Role of Taurine

Extensive application of pesticides is usually accompanied with serious problems of pollution and health hazards. Lambda-cyhalothrin (LCT), a type II synthetic pyrethroid, is widely used in agriculture, home pest control and protection of foodstuff. This study designed to evaluate the dose dependent haematological, hepatic and gonadal toxicity of LCT at different dose levels in Wistar rat. Investigations were also done to find out the toxic effect of lambda cyhalothrin on lipid metabolism in female rat and its amelioration by taurine. Rats were exposed to different doses of lambda cyhalothrin over a period of 14 consecutive days. Exposure to LCT produced ataxia, agitation, rolling and also tremors which were considered as the signs of toxicity. Significant decrease in erythrocyte count, haemoglobin percentage, seminal fructose concentration, hepatic and testicular reduced glutathione (GSH) content was observed. Increase in leukocyte count, serum aspartic and alanine transaminase, hepatic and testicular malondialdehyde (MDA), testicular and ovarian cholesterol after LCT treatment were seen in male rats at the dose level of 10.83 mg/kg body wt. (1/7th LD50). Elevated ovarian cholesterol and MDA and reduced 3β hydroxy steroid dehydrogenase (HSD) and GSH level were also observed in lambda cyhalothrin exposed female rat at the dose level of 6.29 mg/kg body wt. (1/9th LD50). LCT caused increase in serum triglyceride, cholesterol, low density lipoproteins (LDL), very low density lipoproteins (VLDL) and bilirubin and decrease in serum high density lipoproteins (HDL) in female rat. Taurine pretreatment ameliorated LCT induced altered lipid metabolic biomarkers in female rat.

Sub-Acute Toxicity Study of Calotropis gigantea Latex Extracts in Male Swiss Albino Mice

Background: Calotropis gigantea of family Asclepiadaceae, is traditionally used in ayurveda for its anti-helminthic, anti-pyretic, and anti-malarial activities. The present study was designed to investigate the sub-acute toxic effects of ethanol and methanol extract of Calotropis gigantea latex in mouse model using haematology, serum biochemistry and histopathological changes as toxicity indices. Methods: In the sub-acute 28-day toxicity study, ethanol and methanol extract of Calotropis gigantea latex were administered intraperitoneally at the dose levels of 50, 100, 200, 500, 1000 and 2000 mg/kg body wt./day. Results: Significant (p>0.05) difference were not observed in relative organ weights and haematological, hepatic and renal biomarkers up to the dose level of 500 mg/kg body wt./day for 28 days except blood glucose and serum glutamate pyruvate transaminase (SGPT) in comparison to the control group. No significant toxicity was seen up to the dose level of 1000 mg/kg body wt./day for 28 days in case of blood glucose and SGPT. Conclusion: The findings suggest that Calotropis gigantea latex extracts do not cause subacute toxicity up to the level of 1000 mg/kg body wt./day for 28 days and may be considered as phytomedicinal therapeutic agents.

Antigonadal and endocrine-disrupting activities of lambda cyhalothrin in female rats and its attenuation by taurine:

Lambda cyhalothrin (LCT) is a type II pyrethroid with a wide range of agricultural, industrial, and household uses. Taurine is a nonprotein sulfur containing amino acid as well as a well-known antioxidant and has valuable clinical applications in the detoxification of xenobiotics. The present study evaluated the effect of LCT on the reproductive and endocrine systems of female rats and determined whether taurine might alter these effects. Sexually mature female rats were administered LCT at two different dosages (6.3 mg/kg BW and 11.33 mg/kg BW) once daily by oral gavage for 14 consecutive days with the pretreatment of taurine (50 mg kg−1 BW). LCT treatment resulted in diminished adrenal cholesterol, ovarian 3β- and 17β-hydroxysteroid dehydrogenase (HSD) activity with increased ovarian cholesterol, adrenal 3β- and 17β-HSD activity. Furthermore, protein and mRNA expressions of ovarian 17β-HSD and steroidogenic acute regulatory protein were also decreased. Hormonal imbalance was evident by concurrent reduction in the gonadotropic hormone, estradiol, and progesterone levels in LCT-treated rats. These rats also demonstrated the histopathological evidence of degenerative changes in the ovaries. Pretreatment of taurine attenuated the LCT-induced changes.

Dose-Dependent Hematological, Hepatic and Gonadal Toxicity of Cypermethrin in Wistar Rats

Background: Pesticides are used frequently and may have various adverse effects on human health in different ways. Cypermethrin (CYP) is a synthetic type II pyrethroid pesticide that has been used extensively to control a wide variety of pests in agriculture, forestry, horticulture, and public health. Objectives: This study aimed to investigate the dose-dependent hematological, hepatic and gonadal toxicity of CYP in mature male and female Wistar rats. Methods: Rats were randomly divided into nine groups, different doses of CYP were administered for 14 consecutive days and different hematological, hepatic and gonadal parameters were assayed. Results: Erythrocyte count, hemoglobin percentage, hepatic reduced glutathione (GSH) content and sperm count were significantly diminished. Serum aspartic and alanine transaminase, hepatic malondialdehyde (MDA), testicular cholesterol content were increased following CYP treatment in male rats at 40 and 80 mg/kg body weight (1/9 and 1/4.5 LD50). Elevated ovarian cholesterol content and decreased 17β hydroxy steroid dehydrogenase (HSD) levels were also observed in CYP-exposed female rats at a dose level of 34.33 and 51.5 mg/kg body wt. (1/9 and 1/6 LD50). Conclusion: Taken together, CYP initiated hematological, hepatic and gonadal toxicity in mature male rats with a body weight of 40 mg/kg (1/9 LD50) and gonadal toxicity in mature female rats with a body weight of 34.33 mg/kg (1/9 LD50) and above.

Mycotoxin MT81 and Its Benzoylated Derivative Exhibit Potential Antisteroidogenic Activities In Prepubertal Female Wistar Rat

MT81, a mycotoxin (polyhydroxyanthraquinone, Molecular formula C22 H18 O7) was isolated and identified from Penicillium nigricans. It is highly toxic (LD50 value is 35.1 mg/kg body weight) and shows antimicrobial, antileishmanial activities and produces hepato-renal dysfunction and hematological disorders. The benzoylated derivative of MT81 was synthesized in our laboratory and its LD50 value is 87.1 mg/kg body weight. In spite of its reduced toxicity, the benzoylated derivative (BzMT81) shows potent antimicrobial effects. The present study was aimed to investigate the antifertility activities of Mycotoxin MT81 and its benzoylated derivative on the reproductive system of female prepubertal albino Wistar rats. MT81 and BzMT81 arrested vaginal opening, reduced body weight and the weights of ovaries and uterus. Total cholesterol and ascorbic acid content of the ovaries were elevated whereas the activities of ∆5-3β-hydroxysteroid dehydrogenase and glucose-6-phosphate dehydrogenase were decreased in a dose-dependent manner. In the adrenal gland of rat these parameters showed opposite findings. The study reveals that MT81 and BzMT81 both inhibit ovarian steroidogenesis and causes ovarian sterility in female prepubertal rat but the analogue shows more potentiality.

Effects of Exposure to Cypermethrin on the Onset of Puberty and Ovarian Biomarkers in Female Prepubertal Rat: Attenuating Role of Zinc

Cypermethrin, a synthetic pyrethyroid pesticide, is used for more than one decade to control a wide variety of pests in agriculture. The present study designed to evaluate the protective role of zinc in attenuating cypermethrin induced reproductive toxicity in female prepubertal rat. Female prepubertal rat received oral cypermethrin alone at two dose levels and zinc alone or combined with cypermethrin for consecutive 14 days. Cypermethrin arrested vaginal opening, reduced the weights of ovaries and uterus. Total cholesterol and ascorbic acid content of the ovaries were elevated whereas the activities of Δ5,3β-hydroxysteroid dehydrogenase and 17 β-hydroxysteroid dehydrogenase were decreased in a dose-dependent manner. In the adrenal gland of rat these parameters showed opposite findings. The levels of serum LH, FSH and estradiol were also decreased. Cypermethrin treatment also produced oxidative stress in ovary by significant increase in malondialdehyde level, accompanied by a reduction in reduced glutathione and antioxidant enzymes. From the results, we may conclude that cypermethrin suppresses the female reproductive functions in rat by disrupting the estrous cycle and ovarian biomarkers by increasing oxidative stress and zinc attenuates the cypermethrin-induced toxicity.