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LanguagesEnglish, Bengali
Publications (6) View all
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Article: Doxorubicin-induced neurotoxicity is attenuated by a 43-kD protein from the leaves of Cajanus indicus L. via NF-κB and mitochondria dependent pathways.
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ABSTRACT: Doxorubicin (Dox) is an effective anthracycline antitumour drug although its clinical efficacy is restricted because of several acute and chronic side effects. It has been suggested that Dox-induced anticancer effect and neurotoxicity do not follow identical mechanism. The present study has been carried out to investigate the neuroprotecive role of a 43-kD protein (Cajanus indicus (CI) protein) against Dox-induced oxidative impairment and brain tissue damage. Administration of Dox (25 mg/kg body weight) increased reactive oxygen species (ROS) production, altered neuro antioxidant status, activities of brain specific coenzymes (like acetyl coenzyme, monoamine oxidase, etc.), ATPases (like Na(+)/K(+), Ca(2+), etc.) and brain biogenic amines levels. Signal transduction studies showed that Dox markedly decreased mitochondrial membrane potential, disturbed Bcl-2 family protein balance, enhanced cytochrome c release in the cytosol, increased levels of Apaf1, caspase-9/3, cleaved PARP protein and ultimately led to apoptotic cell death. In addition, Dox markedly increased nuclear factor kappa B (NF-κB) nuclear translocation in association with IKKα/β phosphorylation and IκBα degradation. Post-treatment with CI protein (3 mg/kg body weight, once daily for next 4 days), however, reduced Dox-induced oxidative stress, attenuated the nuclear translocation of NF-κB and protected the brain tissue from Dox-induced apoptotic death. Histological studies also support these experimental findings. Results suggest that CI protein might act as a beneficial agent against Dox-induced neuronal dysfunctions.Free radical research 03/2012; 46(6):785-98. · 2.22 Impact Factor -
Article: Traditional extract of Pithecellobium dulce fruits protects mice against CCl(4) induced renal oxidative impairments and necrotic cell death.
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ABSTRACT: The present study has been carried out to investigate the role of the aqueous extract of the fruits of Pithecellobium dulce (AEPD) against carbon tetrachloride (CCl(4)) induced renal oxidative injury in mice. HPLC analysis shows that AEPD contains phenolics, flavonoids and saponins as the major active components. Creatinine and blood urea nitrogen (BUN) levels were assayed to determine renal protective action of AEPD in CCl(4)-induced renal pathophysiology. Its antioxidant activity was determined by measuring radical scavenging activity, antioxidant enzymes activities, GSH content, protein carbonylation and lipid peroxidation. In addition, FACS analysis, DNA fragmentation and histological studies were carried out to determine its effect in CCl(4) induced renal oxidative injury and cell death. CCl(4) exposure increased the intracellular reactive oxygen species production, decreased intracellular antioxidant defence, reduced mitochondrial membrane potential, attenuated the intracellular ATP content and caused renal cell death mainly via the necrotic pathway as revealed by DNA fragmentation analysis. Treatment with AEPD both prior and post to the toxin exposure protected the organ from CCl(4) induced oxidative insult. Histological studies also support our results. Combining, results suggest that the protective role of AEPD against CCl(4) induced renal oxidative impairments is probably due to the antioxidative properties present in its active constituents.Pathophysiology 03/2012; 19(2):101-14. -
Article: A 43 kD protein from the leaves of the herb Cajanus indicus L. modulates doxorubicin induced nephrotoxicity via MAPKs and both mitochondria dependent and independent pathways.
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ABSTRACT: Doxorubicin (Dox), a chemotherapeutic drug, is used for the treatment of different types of cancers. Application of this drug has now been made limited because of its several acute and chronic side effects. The aim of this work is to investigate the nephroprotecive role of a 43 kD protein (CI protein) isolated from the leaves of Cajanus indicus L, against Dox-induced oxidative impairment and kidney tissue damage. Administration of Dox (20 mg/kg body weight, once) significantly enhanced levels of blood urea nitrogen (BUN), creatinine, uric acid, TNF-α, urinary γ-glutamyl transpeptidase (γ-GT) activity, total urinary protein and urinary glucose level. Moreover, Dox exposure increased intracellular ROS production, lipid peroxidation, protein carbonylation and ATPases (like Na(+)/K(+), Mg(2+).) activities. On the other hand, the same exposure decreased GSH level and the activities of antioxidant enzymes; indicating that Dox-induced renal damage was mediated via oxidative stress. Signal transduction studies showed that Dox markedly decreased mitochondrial membrane potential, disturbed Bcl-2 family protein balance, enhanced cytochrome c release in the cytosol, increased levels of Apaf1, caspase-9/3/8, FAS, cleaved PARP protein and ultimately led to apoptotic cell death. In addition, Dox distinctly increased the phosphorylation of p38, JNK and ERK MAPKs. Post treatment with CI protein (3 mg/kg body weight, once daily for 4 days), however, reduced Dox-induced oxidative stress and suppressed all these apoptotic events. Histological studies also support the beneficial role of the CI protein in this organ pathophysiology. Combining, results suggest that CI protein might act as a beneficial agent in Dox-induced renal dysfunctions.Biochimie 03/2012; 94(6):1356-67. · 3.02 Impact Factor -
Article: Involvement of both intrinsic and extrinsic pathways in hepatoprotection of arjunolic acid against cadmium induced acute damage in vitro.
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ABSTRACT: Cadmium (Cd) is one of the ubiquitous environmental pollutants and is responsible for various organ pathophysiology including hepatic disorders. It is extremely toxic even in low concentrations and bioaccumulate in organisms. The present study has been carried out to investigate the cytoprotective role of arjunolic acid (AA), a tri terpenoid saponin, against Cd induced oxidative impairment and cell death in murine hepatocytes. Administration of cadmium (30 μM), in the form of chloride (CdCl(2)) for 2h, significantly enhanced the ALT, ALP and LDH leakage, increased reactive oxygen species (ROS) production, reduced hepatocytes viability and altered the antioxidant status of hepatocytes by reducing intracellular GSH level, anti-oxidant enzymes activity and increasing intracellular GSSG and lipid peroxidation. Evidence for Cd-induced nature of cell death was sought by flow cytometric analysis. Signal transduction studies revealed that Cd markedly increased the levels of caspase-9, -8, -3, Fas and Bid, decreased mitochondrial membrane potential, enhanced cytochrome c release in the cytosol, disturbed the Bcl-2 family protein balance, cleaved PARP protein and ultimately led to apoptotic cell death. Results showed that Cd could trigger both intrinsic and extrinsic apoptotic pathways. In addition, Cd markedly increased NF-κB nuclear translocation in association with IKKα/β phosphorylation and IκBα degradation. Simultaneous treatment with AA (200 μM), however, reduced Cd-induced oxidative stress, attenuated the nuclear translocation of NF-κB and protects the hepatocytes from Cd-induced apoptotic death. Combining, data suggest that Cd-induced hepatic dysfunction and apoptosis might be supported by the ROS formation and mediated via the activation of NF-κB. AA treatment, on the other hand, reduced Cd-induced oxidative stress, attenuated the activation of NF-κB and mitochondrion-dependent and independent apoptotic signaling pathways.Toxicology 03/2011; 283(2-3):129-39. · 3.68 Impact Factor -
Article: Modulation of mercury-induced mitochondria-dependent apoptosis by glycine in hepatocytes.
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ABSTRACT: Mercury (Hg) is one of the universal environmental pollutants and is responsible for various organ pathophysiology including oxidative stress-induced hepatic disorders. In the present study, we aimed to explore the protective role of glycine in Hg-induced cytotoxicity and cell death in murine hepatocytes. Exposure of mercury (20 μM), in the form HgCl2 for 1 h, significantly enhanced the ALT and ALP leakage, increased reactive oxygen species production, reduced cell viability and distorted the antioxidant status of hepatocytes. Flow cytometric analyses shows that Hg-induced apoptotic death in hepatocytes. Mechanism of this pathophysiology involves reduced mitochondrial membrane potential, variations in Bcl-2/Bad proteins, activation of caspases and cleavage of PARP protein. In addition, Hg distinctly increased NF-κB phosphorylation in association with IKKα phosphorylation and IκBα degradation. Concurrent treatment with glycine (45 mM), however, reduced Hg-induced oxidative stress, attenuated the changes in NF-κB phosphorylation and protects hepatocytes from Hg-induced apoptotic death. Hg also distinctly increased the phosphorylation of p38, JNK and ERK mitogen-activated protein kinase (MAPKs). Glycine treatment suppressed these apoptotic events, signifying its protective role in Hg-induced hepatocyte apoptosis as referred by reduction of p38, JNK and ERK MAPK signaling pathways. Results suggest that glycine can modulate Hg-induced oxidative stress and apoptosis in hepatocytes probably because of its antioxidant activity and functioning via mitochondria-dependent pathways and could be a beneficial agent in oxidative stress-mediated liver diseases.Amino Acids 03/2011; 42(5):1669-83. · 3.25 Impact Factor
