Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats / Mitigação da nefrotoxicidade induzida pela cisplatina pela casticina em ratos albinos machos

Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

A cisplatina (CP) é uma droga antineoplásica poderosa, comumente usada, com vários efeitos colaterais. Casticin (CAS) é considerado um eliminador de radicais livres e um potente antioxidante. A presente pesquisa foi planejada para avaliar o potencial curativo da CAS em lesão renal induzida por PC em ratos albinos machos. Vinte e quatro ratos albinos machos foram distribuídos em quatro grupos iguais. O Grupo 1 foi considerado grupo controle. Os animais do Grupo 2 foram injetados com 5 mg / kg de PB por via intraperitoneal. O Grupo 3 foi cotratado com CAS (50 mg / kg) por via oral e injeção de CP (5 mg / kg). O Grupo 4 foi tratado com CAS (50 mg / kg) por via oral durante todo o experimento. A administração de CP reduziu substancialmente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa S-transferase (GST), glutationa redutase (GSR), glutationa (GSH), enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e níveis de peróxido de hidrogênio (H2O2). Os níveis de ureia, creatinina urinária, urobilinogênio, proteínas urinárias, molécula 1 de lesão renal (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina e a depuração da creatinina foram significativamente reduzidas no grupo tratado com PC. Os resultados demonstraram que a CP aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappa-B (NF-κB), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β), interleucina-6 (IL-6) níveis e atividade da ciclooxigenase-2 (COX-2) e danos histopatológicos. No entanto, a administração de CAS apresentou um efeito paliativo contra a toxicidade renal gerada por CP e recuperou todos os parâmetros, trazendo-os a um nível normal. Estes resultados revelaram que o CAS é um composto eficaz com potencial curativo para combater o dano renal induzido por CP.

Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats

Abstract Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-B), tumor necrosis factor- (TNF-), Interleukin-1 (IL-1), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

Resumo A cisplatina (CP) é uma droga antineoplásica poderosa, comumente usada, com vários efeitos colaterais. Casticin (CAS) é considerado um eliminador de radicais livres e um potente antioxidante. A presente pesquisa foi planejada para avaliar o potencial curativo da CAS em lesão renal induzida por PC em ratos albinos machos. Vinte e quatro ratos albinos machos foram distribuídos em quatro grupos iguais. O Grupo 1 foi considerado grupo controle. Os animais do Grupo 2 foram injetados com 5 mg / kg de PB por via intraperitoneal. O Grupo 3 foi cotratado com CAS (50 mg / kg) por via oral e injeção de CP (5 mg / kg). O Grupo 4 foi tratado com CAS (50 mg / kg) por via oral durante todo o experimento. A administração de CP reduziu substancialmente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa S-transferase (GST), glutationa redutase (GSR), glutationa (GSH), enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e níveis de peróxido de hidrogênio (H2O2). Os níveis de ureia, creatinina urinária, urobilinogênio, proteínas urinárias, molécula 1 de lesão renal (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina e a depuração da creatinina foram significativamente reduzidas no grupo tratado com PC. Os resultados demonstraram que a CP aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappa-B (NF-B), fator de necrose tumoral- (TNF-), interleucina-1 (IL-1), interleucina-6 (IL-6) níveis e atividade da ciclooxigenase-2 (COX-2) e danos histopatológicos. No entanto, a administração de CAS apresentou um efeito paliativo contra a toxicidade renal gerada por CP e recuperou todos os parâmetros, trazendo-os a um nível normal. Estes resultados revelaram que o CAS é um composto eficaz com potencial curativo para combater o dano renal induzido por CP.

Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats.

Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

Histopathological alterations in gills, liver, kidney and muscles of Ictalurus punctatus collected from pollutes areas of River / Alterações histopatológicas em brânquias, fígado, rim e músculos de Ictalurus punctatus coletados em áreas poluídas do rio

Abstract Untreated sewage and industrial wastes from Faisalabad city are disposed to River Chenab through Chakbandi Main Drain (CMD). The present project is planned to investigate the effects of this freshwater pollution on the body of fish Ictalurus punctatus. The specimens of this fish species were collected upstream and downstream of the entrance of CMD into River Chenab. Fish gills, liver, kidney and muscles from dorsolateral regions of fish were subjected to histopathology. Farmed fish and fish from upstream areas were used as control. Fish collected from polluted experimental sites showed significant damage in selected organs. Gill tissues showed an abnormality in the form of an uplifting of the primary epithelium, fusion, vacuolation, hypertrophy, and necrosis. While liver tissues subjected to hepatocytes degeneration, necrosis, mitochondrial granular hepatocyte, and sinusoids dilation. Kidney tissues indicated increased bowmen space and constricted glomerulus and degenerated nephrons. Edema, necrosis, and atrophy were observed in muscle tissues of fish from polluted areas. Fish from the upstream area showed fused gill lamellae, inflammatory cell infiltration, hypertrophy and vacuolation in hepatocytes. Kidney tissues indicated the presence of nuclear tubular cells, destructive renal tubules, hemorrhage, and necrosis at tubular epithelium. Intra myofibril spaces were also observed in muscles. Specimens of control fish indicated no variation in gills, liver, kidney, and muscles. The present study revealed a strong correlation between the degree of tissue damage and environmental contamination. Present findings also compel global warnings to protect our water bodies and fish to rescue the human population.

Resumo O esgoto não tratado e os resíduos industriais da cidade de Faisalabad, no Paquistão, são descartados no Rio Chenab através do dreno principal de Chakbandi (CMD). O presente projeto busca investigar os efeitos dessa poluição de água doce no corpo de peixes Ictalurus punctatus. Os espécimes deste peixe foram coletados a montante e a jusante da entrada do CMD no Rio Chenab. Brânquias, fígado, rim e músculos das regiões dorsolaterais dos peixes foram submetidos à histopatologia. Peixes de criação e peixes de áreas a montante foram utilizados como controle. Peixes coletados em locais experimentais poluídos mostraram danos significativos em órgãos selecionados. Os tecidos branquiais mostraram uma anormalidade na forma de elevação do epitélio primário, fusão, vacuolação, hipertrofia e necrose. Observou-se que os tecidos hepáticos estão sujeitos a degeneração de hepatócitos, necrose, hepatócitos mitocondriais granulares e dilatação de sinusoides. Os tecidos renais indicaram aumento do espaço dos arqueiros, glomérulos contraídos e néfrons degenerados. Edema, necrose e atrofia foram observados nos tecidos musculares de peixes de áreas poluídas. Peixes da área a montante apresentaram lamelas branquiais fundidas, infiltração de células inflamatórias, hipertrofia e vacuolização em hepatócitos. Os tecidos renais indicaram a presença de células tubulares nucleares, túbulos renais destrutivos, hemorragia e necrose no epitélio tubular. Os espaços intramiofibrilas também foram observados nos músculos. Amostras de peixes controle não indicaram variação em brânquias, fígado, rim e músculos. O presente estudo revelou uma forte correlação entre o grau de dano tecidual e a contaminação ambiental. As descobertas atuais também constituem avisos globais para proteger nossos corpos d'água e peixes para resguardar a população humana.

Histopathological alterations in gills, liver, kidney and muscles of Ictalurus punctatus collected from pollutes areas of River.

Untreated sewage and industrial wastes from Faisalabad city are disposed to River Chenab through Chakbandi Main Drain (CMD). The present project is planned to investigate the effects of this freshwater pollution on the body of fish Ictalurus punctatus. The specimens of this fish species were collected upstream and downstream of the entrance of CMD into River Chenab. Fish gills, liver, kidney and muscles from dorsolateral regions of fish were subjected to histopathology. Farmed fish and fish from upstream areas were used as control. Fish collected from polluted experimental sites showed significant damage in selected organs. Gill tissues showed an abnormality in the form of an uplifting of the primary epithelium, fusion, vacuolation, hypertrophy, and necrosis. While liver tissues subjected to hepatocytes degeneration, necrosis, mitochondrial granular hepatocyte, and sinusoids dilation. Kidney tissues indicated increased bowmen space and constricted glomerulus and degenerated nephrons. Edema, necrosis, and atrophy were observed in muscle tissues of fish from polluted areas. Fish from the upstream area showed fused gill lamellae, inflammatory cell infiltration, hypertrophy and vacuolation in hepatocytes. Kidney tissues indicated the presence of nuclear tubular cells, destructive renal tubules, hemorrhage, and necrosis at tubular epithelium. Intra myofibril spaces were also observed in muscles. Specimens of control fish indicated no variation in gills, liver, kidney, and muscles. The present study revealed a strong correlation between the degree of tissue damage and environmental contamination. Present findings also compel global warnings to protect our water bodies and fish to rescue the human population.

Sub-lethal effect of synthetic pyrethroid pesticide on metabolic enzymes and protein profile of non-target Zebra fish, Danio rerio.

Extensive application of pesticide in agricultural field affects the enzymatic activity of non-target animals, including fishes. In this study, the impact of sublethal concentration of fenvalerate on marker enzymes of freshwater Zebra fish was evaluated. Pesticide-induced stress can specifically affect non target fishes, through elevated level of reactive oxygen species which is responsible for biochemical, cell metabolism and physiological activities. The oxidative stress mediated by fenvalerate at sub lethal concentrations after 28 days of exposure of Zebra fish. Following 28 days of exposure of pesticide, catalase, superoxide dismutase, aspartate amino transferases, alanine amino transferase, alkaline phosphatase and acid phosphatase were assessed. Results revealed reduction of superoxide dismutase activity after 28 days of exposure in sub lethal concentration of fenvalerate in liver and gills. In liver, catalase activity was found to be less in fenvalerate exposed fish than control fish. In liver, increase of 75.75% aspartate amino transferase and 38% increase in alanine amino transferase in gills. SGPT activity was relatively higher than SGOT suggests more contribution of phyruvalate than oxaloacetate formation. Fenvalerate induced changes in acid phosphatase and alkaline phosphatase activity in the liver and gills of Zebra fish after four weeks of exposure. Fenvalerate induced expression of various stress proteins in gill, liver, followed by muscle. Some proteins lost its intensity due to fenvalerate toxicity. Result revealed that enzyme assays and SDS-PAGE analysis for protein subunits determination is relevant tool to monitor stress in freshwater ecosystem. The findings suggest that in monitoring fenvalerate toxicity programme, enzyme activities can be potent diagnostic tool for fenvalerate induced toxicity.

Histopathological alterations in gills, liver, kidney and muscles of Ictalurus punctatus collected from pollutes areas of River

Abstract Untreated sewage and industrial wastes from Faisalabad city are disposed to River Chenab through Chakbandi Main Drain (CMD). The present project is planned to investigate the effects of this freshwater pollution on the body of fish Ictalurus punctatus. The specimens of this fish species were collected upstream and downstream of the entrance of CMD into River Chenab. Fish gills, liver, kidney and muscles from dorsolateral regions of fish were subjected to histopathology. Farmed fish and fish from upstream areas were used as control. Fish collected from polluted experimental sites showed significant damage in selected organs. Gill tissues showed an abnormality in the form of an uplifting of the primary epithelium, fusion, vacuolation, hypertrophy, and necrosis. While liver tissues subjected to hepatocytes degeneration, necrosis, mitochondrial granular hepatocyte, and sinusoids dilation. Kidney tissues indicated increased bowmen space and constricted glomerulus and degenerated nephrons. Edema, necrosis, and atrophy were observed in muscle tissues of fish from polluted areas. Fish from the upstream area showed fused gill lamellae, inflammatory cell infiltration, hypertrophy and vacuolation in hepatocytes. Kidney tissues indicated the presence of nuclear tubular cells, destructive renal tubules, hemorrhage, and necrosis at tubular epithelium. Intra myofibril spaces were also observed in muscles. Specimens of control fish indicated no variation in gills, liver, kidney, and muscles. The present study revealed a strong correlation between the degree of tissue damage and environmental contamination. Present findings also compel global warnings to protect our water bodies and fish to rescue the human population.

Resumo O esgoto não tratado e os resíduos industriais da cidade de Faisalabad, no Paquistão, são descartados no Rio Chenab através do dreno principal de Chakbandi (CMD). O presente projeto busca investigar os efeitos dessa poluição de água doce no corpo de peixes Ictalurus punctatus. Os espécimes deste peixe foram coletados a montante e a jusante da entrada do CMD no Rio Chenab. Brânquias, fígado, rim e músculos das regiões dorsolaterais dos peixes foram submetidos à histopatologia. Peixes de criação e peixes de áreas a montante foram utilizados como controle. Peixes coletados em locais experimentais poluídos mostraram danos significativos em órgãos selecionados. Os tecidos branquiais mostraram uma anormalidade na forma de elevação do epitélio primário, fusão, vacuolação, hipertrofia e necrose. Observou-se que os tecidos hepáticos estão sujeitos a degeneração de hepatócitos, necrose, hepatócitos mitocondriais granulares e dilatação de sinusoides. Os tecidos renais indicaram aumento do espaço dos arqueiros, glomérulos contraídos e néfrons degenerados. Edema, necrose e atrofia foram observados nos tecidos musculares de peixes de áreas poluídas. Peixes da área a montante apresentaram lamelas branquiais fundidas, infiltração de células inflamatórias, hipertrofia e vacuolização em hepatócitos. Os tecidos renais indicaram a presença de células tubulares nucleares, túbulos renais destrutivos, hemorragia e necrose no epitélio tubular. Os espaços intramiofibrilas também foram observados nos músculos. Amostras de peixes controle não indicaram variação em brânquias, fígado, rim e músculos. O presente estudo revelou uma forte correlação entre o grau de dano tecidual e a contaminação ambiental. As descobertas atuais também constituem avisos globais para proteger nossos corpos d'água e peixes para resguardar a população humana.