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1.
Alcohol ; 25(2): 89-97, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11747978

RESUMEN

Ethanol consumption and cigarette smoking are common in societies worldwide and have been identified as injurious to human health. This study was undertaken to examine the interactive effects of chronic ethanol and nicotine consumption on the antioxidant defense system in different tissues of rat. Male Fisher-344 rats were divided into four groups of five animals each and treated for 6.5 weeks as follows: (1) Control rats were administered normal saline orally; (2) ethanol (20% [wt./vol.]) was given orally at a dose of 2 g/kg; (3) nicotine was administered subcutaneously at a dose of 0.1 mg/kg; and (4) a combination of ethanol plus nicotine was administered by the route and at the dose described above. The animals were killed 20 h after the last treatment, and liver, lung, kidney, and testes were isolated and analyzed. Chronic ingestion of ethanol resulted in a significant depletion of glutathione (GSH) content in liver, lung, and testes, whereas chronic administration of nicotine significantly depleted GSH content in liver and testes. The combination of ethanol plus nicotine resulted in a significant depletion of GSH content in liver, lung, and testes. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly increased superoxide dismutase (SOD) activity in liver and decreased SOD activity in kidney. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly decreased catalase (CAT) activity in liver and increased CAT activity in kidney and testes. Chronic ingestion of ethanol resulted in a significant decrease in glutathione peroxidase (GSH-Px) activity in liver and kidney, whereas a combination of ethanol plus nicotine increased GSH-Px activity in liver and decreased GSH-Px activity in kidney and testes. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly increased lipid peroxidation, respectively, in liver. It is suggested that prolonged exposure to ethanol and nicotine produce similar, and in some cases additive, oxidative tissue injuries in rat.


Asunto(s)
Antioxidantes/metabolismo , Depresores del Sistema Nervioso Central/farmacología , Etanol/farmacología , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , Animales , Catalasa/metabolismo , Interacciones Farmacológicas/fisiología , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/fisiología , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Ratas , Ratas Endogámicas F344 , Superóxido Dismutasa/metabolismo
2.
J Appl Toxicol ; 21(4): 341-8, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11481669

RESUMEN

Pyridostigmine bromide (PB), a reversible anticholinesterase drug, had been used against possible nerve gas exposure during the Persian Gulf War. The Gulf War veterans used PB and they were under physical stress. This study investigated the delayed and interactive effects of pyridostigmine and physical stress on the antioxidant defense system in triceps muscle of mice. Male NIH Swiss mice were divided into four groups and treated as follows: sedentary control; pyridostigmine (1.2 mg kg(-1) p.o.); exercise; and PB plus exercise. Mice were exercised for 10 weeks, but PB was administered daily during the 5th and 6th weeks. Mice were sacrificed 24 h after the last treatments and the triceps muscle was isolated and analyzed. There was a significant increase in total superoxide dismutase (CuZn-SOD + Mn-SOD) activity (141% of control) with PB plus exercise, suggesting that any influx of superoxide anions was scavenged efficiently. The Mn-SOD enzyme protein levels were reduced significantly (63% of control) by PB plus exercise. Catalase enzyme protein levels were increased significantly by exercise (132% of control) as well as by PB plus exercise (139% of control). Glutathione levels were increased significantly by exercise alone (123% of control). Pyridostigmine bromide plus exercise significantly increased the malondialdehyde concentration (124% of control) in the triceps muscle, indicating an oxidative stress response of the combination. The data indicate that a combination of PB ingestion and exercise training significantly altered the antioxidant enzyme activities, enzyme protein levels and lipid peroxidation, leading to oxidative injury. Physical stress amplified the delayed effects of PB in the skeletal muscle of mice.


Asunto(s)
Antioxidantes/metabolismo , Inhibidores de la Colinesterasa/farmacología , Músculo Esquelético/efectos de los fármacos , Bromuro de Piridostigmina/farmacología , Estrés Fisiológico/enzimología , Animales , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Ensayo de Inmunoadsorción Enzimática , Disulfuro de Glutatión/efectos de los fármacos , Disulfuro de Glutatión/metabolismo , Glutatión Peroxidasa/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/efectos de los fármacos , Glutatión Reductasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Ratones , Músculo Esquelético/enzimología , Condicionamiento Físico Animal/fisiología , Esfuerzo Físico/fisiología , Estrés Fisiológico/metabolismo , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Factores de Tiempo
3.
Hear Res ; 159(1-2): 14-22, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11520631

RESUMEN

Carboplatin is currently being used in the clinic against a variety of human cancers. However, high dose carboplatin chemotherapy resulted in ototoxicity in cancer patients. This is the first study to show carboplatin-induced oxidative stress response in the cochlea of rat. Male Wistar rats were divided into two groups of six animals each and treated as follows: (1) control (normal saline, i.p.) and (2) carboplatin (256 mg/kg, i.p.). Animals in both groups were sedated with ketamine/xylazine and auditory brainstem-evoked responses were recorded before and 4 days after treatments. The animals were sacrificed on the fourth day and cochleae were harvested and analyzed. A significant elevation of the hearing threshold shifts was noted at clicks, 8, 16, and 32 kHz tone burst stimuli following carboplatin administration. Carboplatin significantly increased nitric oxide and malondialdehyde levels, xanthine oxidase and manganese-superoxide dismutase activities in the cochlea indicating enhanced flux of free radicals. Cochlear glutathione levels, antioxidant enzyme activities such as copper zinc-superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase and enzyme protein levels were significantly depleted 4 days after carboplatin treatment. The data suggest that carboplatin induced free radical generation and antioxidant depletion, and caused oxidative injury in the cochleae of rats.


Asunto(s)
Antineoplásicos/toxicidad , Carboplatino/toxicidad , Cóclea/efectos de los fármacos , Cóclea/metabolismo , Estrés Oxidativo/efectos de los fármacos , Animales , Antineoplásicos/administración & dosificación , Antioxidantes/metabolismo , Umbral Auditivo/efectos de los fármacos , Carboplatino/administración & dosificación , Catalasa/antagonistas & inhibidores , Cóclea/lesiones , Cóclea/fisiopatología , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Radicales Libres/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/antagonistas & inhibidores , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Óxido Nítrico/metabolismo , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo
4.
Hear Res ; 151(1-2): 71-78, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11124453

RESUMEN

Carboplatin, a platinum-containing anticancer drug, is currently being used against a variety of cancers. However, a single high dose of carboplatin is ototoxic in cancer patients. This is the first study to show carboplatin-induced hearing loss in a rat model. Male Wistar rats were divided into five groups and treated as follows: (1) control (saline, intraperitoneally (i.p.)); (2) carboplatin (64 mg/kg, i.p.); (3) carboplatin (128 mg/kg i.p.); (4) carboplatin (192 mg/kg, i.p.) and (5) carboplatin (256 mg/kg, i.p.). Animals in all groups were sedated with ketamine/xylazine and auditory brain-evoked responses (ABRs) were recorded before and 4 days after treatments. The animals were sacrificed on the fourth day and cochleae were harvested and analyzed. Carboplatin dose-dependently decreased body weight. However, at higher doses of carboplatin (192 and 256 mg/kg), there was a significant elevation of hearing threshold shifts at clicks, 4, 8, 16 and 32 kHz tone burst stimuli. The higher doses of carboplatin (192 and 256 mg/kg) significantly increased cochlear lipid peroxidation (132 and 146% of control) and depleted cochlear glutathione levels (66 and 63% of control), respectively. The antioxidant enzyme activities such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase (GST) depressed significantly at higher doses of carboplatin. The data suggest that higher doses of carboplatin (above 128 mg/kg) induce hearing loss as evidenced by significant changes in ABRs, lipid peroxidation and antioxidants in the cochlea of rats.


Asunto(s)
Antineoplásicos/administración & dosificación , Antineoplásicos/toxicidad , Antioxidantes/metabolismo , Carboplatino/administración & dosificación , Carboplatino/toxicidad , Sordera/inducido químicamente , Animales , Umbral Auditivo/efectos de los fármacos , Catalasa/antagonistas & inhibidores , Cóclea/efectos de los fármacos , Cóclea/metabolismo , Cóclea/fisiopatología , Sordera/metabolismo , Sordera/fisiopatología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/toxicidad , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Glutatión/metabolismo , Glutatión Peroxidasa/antagonistas & inhibidores , Glutatión Reductasa/antagonistas & inhibidores , Glutatión Transferasa/antagonistas & inhibidores , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Ratas , Ratas Wistar , Superóxido Dismutasa/antagonistas & inhibidores
5.
Arch Toxicol ; 74(9): 539-46, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11131034

RESUMEN

In this study, the interactive effects of pyridostigmine, a pretreatment drug against nerve agents, and exercise training on muscle tension were investigated in the mouse lower extremity anterior muscular compartment by dorsiflexion of the foot with stimulation of the peroneal nerve. Acetylcholinesterase (AChE), lipid peroxidation (in terms of the end-product malondialdehyde, MDA) and creatine phosphokinase (CPK) activity in the muscle were correlated with muscle tension. Male NIH Swiss mice were divided into four groups and treated as follows: (1) sedentary control; (2) pyridostigmine (1.2 mg/kg orally) daily for the 5th and 6th weeks; (3) exercise training for 10 weeks; and (4) pyridostigmine plus exercise training for 10 weeks. Experiments on muscle tension were conducted 4 weeks after the last dose of pyridostigmine or saline and 24 h after exercise. The muscle tension was measured in right and left legs using a tension transduction device connected to a polygraph. After muscle tension recording, mice were killed, blood and triceps muscle were isolated, and plasma CPK and muscle AChE activities, and MDA were determined. There was a significant increase in the muscle tension (P<0.05) in the group treated with pyridostigmine plus exercise as compared to the control and exercise groups. The pyridostigmine plus exercise group also showed a significant reduction in AChE activity (P<0.01) and enhanced MDA (P<0.05) in the triceps muscle. These results suggest that subchronic dosages of pyridostigmine and interaction with exercise training result in the delayed effects of reduction in muscle AChE activity and enhanced muscle tension.


Asunto(s)
Acetilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/farmacología , Músculo Esquelético/enzimología , Condicionamiento Físico Animal/fisiología , Bromuro de Piridostigmina/farmacología , Animales , Creatina Quinasa/metabolismo , Estimulación Eléctrica , Pierna/fisiología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Ratones , Contracción Muscular/efectos de los fármacos , Proteínas Musculares/metabolismo , Músculo Esquelético/efectos de los fármacos , Consumo de Oxígeno , Aumento de Peso/efectos de los fármacos
6.
J Appl Toxicol ; 20(4): 327-34, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10942908

RESUMEN

Gulf War veterans were taking pyridostigmine orally against possible exposure to nerve agents as well as being under physical stress. This study was designed to investigate the delayed effects of pyridostigmine and treadmill exercise on cholinesterase activity, lipid peroxidation and histology of peripheral tissues of mice. Male NIH Swiss mice were divided into four groups of 15 animals each and treated as follows: sedentary control; exercise training for 10 weeks; pyridostigmine (1.2 mg kg(-1), p.o.) for 2 weeks during weeks 5 and 6; and pyridostigmine plus exercise training. The mice were sacrificed 24 h after the last exercise, and blood, triceps muscle and sciatic nerve were isolated and analyzed. The group treated with pyridostigmine alone showed decreased plasma butyrylcholinesterase (BChE) activity (87% of control), whereas pyridostigmine plus exercise significantly decreased the BChE activity (79% of control), indicating an interactive effect of the combination. Acetylcholinesterase (AChE) activity did not alter significantly in red blood cells, platelets or sciatic nerve with either of the treatments. However, AChE activity in triceps muscle decreased significantly (78% of control) in the group treated with pyridostigmine plus exercise. Creatine phosphokinase activity in plasma increased slightly (compared to control, pyridostigmine or exercise group) in mice treated with pyridostigmine plus exercise, which may be indicative of perturbation in the integrity of the skeletal muscle due to combination. However, there were no obvious histological abnormalities in the triceps muscle detected between experimental and control groups. Interaction of pyridostigmine and exercise significantly increased the concentration of the end product of lipid peroxidation (malondialdehyde) (124% of control) in triceps muscle, indicating an oxidative stress response of the combination. These results indicate that physical stress enhanced the delayed toxic effects of a subchronic oral dose of pyridostigmine primarily in the skeletal muscle of mice.


Asunto(s)
Inhibidores de la Colinesterasa/toxicidad , Bromuro de Piridostigmina/toxicidad , Estrés Fisiológico/enzimología , Acetilcolinesterasa/efectos de los fármacos , Acetilcolinesterasa/metabolismo , Animales , Butirilcolinesterasa/efectos de los fármacos , Butirilcolinesterasa/metabolismo , Creatina Quinasa/efectos de los fármacos , Creatina Quinasa/metabolismo , Preparaciones de Acción Retardada , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Músculos/efectos de los fármacos , Músculos/enzimología , Condicionamiento Físico Animal/fisiología , Estrés Fisiológico/metabolismo
7.
Pharmacol Toxicol ; 86(5): 234-41, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-10862506

RESUMEN

This study was designed to investigate the role of graded doses of lipoic acid pretreatment against cisplatin-induced nephrotoxicity. Male Wistar rats were divided into six groups and treated as follows: 1) vehicle (saline) control; 2) cisplatin (16 mg/kg, intraperitoneally); 3) lipoic acid (100 mg/kg, intraperitoneally); 4) cisplatin plus lipoic acid (25 mg/kg); 5) cisplatin plus lipoic acid (50 mg/kg) and 6) cisplatin plus lipoic acid (100 mg/kg). Rats were sacrificed three days after treatment, and plasma as well as kidneys were isolated and analyzed. Plasma creatinine increased (677% of control) following cisplatin administration alone which was decreased by lipoic acid in a dose-dependent manner. Cisplatin-treated rats showed a depletion of renal glutathione (GSH), increased oxidized GSH and decreased GSH/GSH oxidized ratio (62%, 166% and 62% of control), respectively which were restored with lipoic acid pretreatment. Renal superoxide dismutase, catalase, glutathione peroxidase (GSH peroxidase) and glutathione reductase activities decreased (62%, 75%, 62% and 80% of control), respectively, and malondialdehyde content increased (204% of control) following cisplatin administration, which were restored with increasing doses of lipoic acid. The renal platinum concentration increased following cisplatin administration, which was possibly decreased by chelation with lipoic acid. The data suggest that the graded doses of lipoic acid effectively prevented a decrease in renal antioxidant defense system and prevented an increase in lipid peroxidation, platinum content and plasma creatinine concentrations in a dose-dependent manner.


Asunto(s)
Antioxidantes/uso terapéutico , Cisplatino/antagonistas & inhibidores , Enfermedades Renales/prevención & control , Riñón/efectos de los fármacos , Ácido Tióctico/uso terapéutico , Animales , Antineoplásicos/antagonistas & inhibidores , Antineoplásicos/toxicidad , Catalasa/metabolismo , Cisplatino/toxicidad , Creatinina/sangre , Relación Dosis-Respuesta a Droga , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Inyecciones Intraperitoneales , Riñón/metabolismo , Enfermedades Renales/sangre , Enfermedades Renales/inducido químicamente , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Platino (Metal)/metabolismo , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo
8.
J Appl Toxicol ; 19(4): 221-8, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10439335

RESUMEN

This study was designed in order to evaluate alterations in the reactive oxygen species (ROS) scavenging system in olfactory bulb, dorsal neocortex and cerebellum for 6 weeks following a single subcutaneous dose (600 mg kg-1) of diethyldithiocarbamate (DDTC) to rats. A single dose of DDTC caused substantial damage to the olfactory epithelium and degeneration within the olfactory bulb. The epithelium regenerates, followed by regeneration in the olfactory bulb. The mean olfactory bulb weight decreased significantly 3 days after DDTC administration and gradually recovered to control values in 6 weeks. The DDTC-induced lesion of the olfactory nerve resulted in significant changes in glutathione (GSH) and antioxidant enzyme activities in olfactory bulb. In contrast, no significant changes were found in either cerebellum or dorsal neocortex. These observations indicate that a single dose of DDTC selectively affected the ROS scavenging system of the olfactory bulb. Moreover, these changes persisted for at least 6 weeks, which includes regeneration and synaptogenesis. Olfactory bulb GSH concentrations decreased significantly by 47 +/- 4%, glutathione reductase activity decreased by 18 +/- 3% and catalase activity increased by 27 +/- 7% over the 6 weeks. Superoxide dismutase activity decreased significantly in olfactory bulb of rats by 32 +/- 6% at 3 days following the lesion and then recovered and increased by 38 +/- 3% at 3 weeks. Olfactory bulb malondialdehyde concentrations were elevated (298 +/- 67%) throughout the post-lesion survival period, although this change did not reach the stringent statistical significance level required in this study. These data suggest that increased ROS flux perturbs the olfactory bulb antioxidant defense system during olfactory nerve regeneration.


Asunto(s)
Antioxidantes/metabolismo , Quelantes/toxicidad , Ditiocarba/toxicidad , Bulbo Olfatorio/efectos de los fármacos , Oxidorreductasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Catalasa/metabolismo , Cerebelo/efectos de los fármacos , Cerebelo/metabolismo , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Inyecciones Subcutáneas , Masculino , Malondialdehído/metabolismo , Neocórtex/efectos de los fármacos , Neocórtex/metabolismo , Regeneración Nerviosa/efectos de los fármacos , Regeneración Nerviosa/fisiología , Bulbo Olfatorio/metabolismo , Bulbo Olfatorio/patología , Nervio Olfatorio/efectos de los fármacos , Nervio Olfatorio/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo
9.
Alcohol ; 18(2-3): 203-14, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10456572

RESUMEN

This study was designed to investigate the dose as well as time dependent effects of ethanol on testicular antioxidant defense system in rats. Male Fischer 344 rats were administered ethanol at a dose of 2, 4, and 6 gm/kg orally and control received equal volume of saline and sacrificed 1 h after ethanol ingestion. For time course study, animals were administered ethanol 4 g/kg orally and sacrificed at 1.5, 2, 4, and 6 h after ethanol ingestion. Testicular ethanol concentration increased with increasing doses of ethanol. Copper zinc-superoxide dismutase (CuZn-SOD) activity significantly decreased in the testes of rats treated with increasing doses of ethanol whereas manganese-superoxide dismutase (Mn-SOD) activity significantly increased in a dose dependent manner (181, 186, and 195% of control, respectively). Testicular glutathione (GSH) and malondialdehyde (MDA) levels did not significantly alter with increasing doses of ethanol one hour after ethanol ingestion. Ethanol concentration decreased in the testes with an increase in time after ethanol ingestion. Testicular CuZn-SOD activity significantly decreased whereas Mn-SOD activity increased with an increase in time after ethanol ingestion. Testicular catalase (CAT) activity significantly decreased at 2 h postethanol ingestion. Testicular MDA levels significantly increased at 4 and 6 h after ethanol ingestion indicating that end product of lipid peroxidation. MDA, takes considerable time to form in the testes. A significant decrease in the ratios of CAT/Mn-SOD and glutathione peroxidase (GSH-Px)/Mn-SOD in the testes of rat suggests the ability of mitochondria to scavenge reactive oxygen species (ROS). It is suggested that antioxidant enzyme ratios may be used as an important parameter to determine ethanol induced oxidative stress in the tissues.


Asunto(s)
Antioxidantes/metabolismo , Depresores del Sistema Nervioso Central/farmacología , Etanol/farmacología , Superóxido Dismutasa/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Depresores del Sistema Nervioso Central/administración & dosificación , Relación Dosis-Respuesta a Droga , Etanol/administración & dosificación , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Masculino , Malondialdehído/metabolismo , Ratas , Ratas Endogámicas F344 , Superóxido Dismutasa/metabolismo , Testículo/metabolismo , Factores de Tiempo
10.
Toxicol Sci ; 47(2): 195-202, 1999 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10220857

RESUMEN

This study investigated the alterations that occur in auditory brainstem-evoked responses (ABRs) concurrent with changes in cochlear concentrations of glutathione (GSH), lipid peroxidation, and antioxidant enzyme activity in cisplatin-induced ototoxicity and in dose-dependent otoprotection by an antioxidant lipoate. Male Wistar rats were divided into different groups and were treated as follows, with: (1) vehicle (saline) control; (2) cisplatin (16 mg/kg, i.p.); (3) lipoate (100 mg/kg, i.p.) plus saline; (4) cisplatin plus lipoate (25 mg/kg); (5) cisplatin plus lipoate (50 mg/kg), and (6) cisplatin plus lipoate (100 mg/kg). Post-treatment ABRs were evaluated after three days, the rats were sacrificed, and cochleae were harvested and analyzed. The cisplatin-injected rats showed ABR threshold elevations above the pre-treatment thresholds. Rats treated with lipoate plus cisplatin did not show significant elevation of hearing thresholds. Cisplatin administration resulted in a depletion of cochlear GSH concentration (69% of control), whereas, cisplatin-plus-lipoate treatment increased GSH concentration close to control value. Cisplatin-treated rats showed a decrease in cochlear superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GR) activities (57, 78, 59, and 58% of control, respectively), and an increase in malondialdehyde (MDA) concentration (196% of control). Cochlear SOD, CAT, GSH-Px, and GR activities and MDA concentrations were restored in the rats injected with cisplatin plus graded doses of lipoate than those with cisplatin alone. It is concluded that cisplatin-induced ototoxicity is related to impairment of the cochlear antioxidant defense system, and the dose-dependent otoprotection conferred by an antioxidant lipoate against cisplatin ototoxicity is associated with sparing of the cochlear antioxidant defense system.


Asunto(s)
Antineoplásicos/toxicidad , Antioxidantes/uso terapéutico , Cisplatino/toxicidad , Cóclea/efectos de los fármacos , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Ácido Tióctico/uso terapéutico , Animales , Antineoplásicos/antagonistas & inhibidores , Antioxidantes/metabolismo , Cisplatino/antagonistas & inhibidores , Cóclea/enzimología , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Radicales Libres , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo
11.
Alcohol ; 17(2): 97-105, 1999 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10064376

RESUMEN

This study investigates the dose- as well as time-dependent effects of ethanol ingestion on antioxidant system and lipid peroxidation in plasma of the rat. The plasma ethanol concentrations were 154+/-18, 231+/-53, and 268+/-49 mg/dl 1 h after oral ethanol doses of 2, 4, and 6 g/kg, respectively. Superoxide dismutase (SOD) (71%, 56%, and 41 % of control) and glutathione reductase (GR) (71%, 66%, and 55% of control) activity in plasma were significantly decreased in a dose-dependent manner. Catalase (CAT)/SOD and glutathione peroxidase (GSH-Px)/SOD ratios were significantly increased whereas GR/GSH-Px ratio was significantly decreased with increasing dose of ethanol. In a time course study, plasma ethanol concentrations were 177+/-9.7, 143+/-11, 99+/-17, and 26+/-11 mg/dl at 1.5, 2, 4, and 6 h after an oral dose (4 g/kg) of ethanol in rat indicating time-dependent elimination of ethanol. Plasma SOD and GSH-Px activity significantly increased 4-6 h whereas GR activity significantly decreased 2-4 h after ethanol ingestion. The ratio of GR/GSH-Px and the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) in plasma decreased at 1.5-6 h after ethanol ingestion. Plasma malondialdehyde (MDA) levels significantly elevated with respect to an increase in time after ethanol ingestion, indicating time-dependent augmentation of lipid peroxidation. The data indicate that ethanol ingestion perturbs the plasma antioxidant system in a dose- and time-dependent manner. The significant changes in the ratios of CAT/SOD, GSH-Px/SOD, GR/GSH-Px, and GSH/GSSG in plasma may be used as an index of alcohol-induced oxidative stress.


Asunto(s)
Antioxidantes/metabolismo , Etanol/administración & dosificación , Animales , Catalasa/sangre , Relación Dosis-Respuesta a Droga , Etanol/sangre , Etanol/farmacología , Glutatión/sangre , Glutatión Peroxidasa/sangre , Glutatión Reductasa/sangre , Cinética , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/sangre , Oxidación-Reducción , Ratas , Ratas Endogámicas F344 , Superóxido Dismutasa/sangre
12.
Neurotoxicology ; 20(6): 977-87, 1999 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10693979

RESUMEN

This study investigated the response of the antioxidant defense system in brain subcellular fractions after oral graded doses of ethanol to rat. Four groups of male Fischer-344 rats were orally administered saline, ethanol 2 g, 4 g, and 6 g/kg, respectively, and sacrificed 1 hour post treatment. Brain cytosol, synaptosomes, microsomes and mitochondria were separated by density gradient differential centrifugation and assayed for antioxidant system. A significant and dose-dependent-decrease in superoxide dismutase (SOD) activity was observed in all brain subcellular fractions. Catalase (CAT) activity was significantly decreased in brain mitochondria (67% and 80% of control) at higher doses of ethanol; whereas, CAT activity was significantly increased in cytosol, synaptosomes and microsomes. Glutathione peroxidase (GSH-Px) activity was significantly increased in all brain subcellular fractions except in cytosol at higher dose of ethanol. Malondialdehyde (MDA) content was significantly increased in all brain subcellular fractions showing dose response of ethanol-induced oxidative stress. The increase in MDA levels in the brain synaptosomes and microsomes were higher at 6 g dose of ethanol (155% and 163% of control) when compared to mitochondria and cytosol. Glutathione (GSH) levels were significantly increased in brain cytosol and microsomes at higher dose of ethanol (164% and 159% of control); whereas, the GSH concentration was significantly decreased in brain synaptosomes and mitochondria. The antioxidant enzyme (AOE) activity ratios (GSH-Px/SOD and GSH-Px + CAT/SOD) were dose dependently increased in all brain subcellular fractions, particularly in synaptosomes. The GSH/GSSG ratio was dose dependently increased in brain microsomes. The perturbations in the antioxidant defense system and enhanced lipid peroxidation following graded doses of ethanol ingestion indicate a dose-dependent-oxidative 2133stress response in brain subcellular compartments of rats.


Asunto(s)
Encéfalo/efectos de los fármacos , Etanol/toxicidad , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Malondialdehído/metabolismo , Animales , Encéfalo/enzimología , Encéfalo/ultraestructura , Catalasa/metabolismo , Citosol/enzimología , Relación Dosis-Respuesta a Droga , Glutatión Peroxidasa/metabolismo , Masculino , Microsomas/enzimología , Mitocondrias/enzimología , Distribución Aleatoria , Ratas , Ratas Endogámicas F344 , Superóxido Dismutasa/metabolismo , Sinaptosomas/enzimología
13.
J Appl Toxicol ; 18(6): 421-9, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9840749

RESUMEN

Recent evidence has indicated that exercise as well as ethanol exerts oxidative stress on vital organs/tissues of the body. However, the combination of both on the testicular antioxidant system is not known. This study investigates the interactive effects of exercise training and chronic ethanol ingestion on the testicular antioxidant system in rats. Male Fisher-344 rats were treated as follows: sedentary control (SC); exercise training (ET) for 6.5 weeks; ethanol (2 g kg(-1), p.o.) for 6.5 weeks; and ET plus ethanol for 6.5 weeks. Exercise training significantly decreased copper-zinc superoxide dismutase (CuZn-SOD) activity and enzyme protein concentration (73% and 67% of SC), whereas manganese SOD (Mn-SOD) and catalase (CAT) activity significantly increased (157% and 141% of SC) in the testes of rat. Exercise training significantly decreased the testicular malondialdehyde (MDA) concentration (70% of SC). Chronic ethanol ingestion significantly decreased testicular CuZn-SOD activity, enzyme protein concentration and CAT activity (65, 70 and 47% of SC) in rats. Ethanol significantly increased the testicular MDA level (129% of SC). The combination of exercise training and chronic ethanol ingestion significantly decreased testicular CuZn-SOD protein, MDA and the reduced glutathione oxidized glutathione ratio (GSH/GSSG) by 62, 70 and 79%, respectively. The data suggest that exercise training provides protection whereas chronic ethanol ingestion exerts oxidative damage to the testes of rat. Exercise training seems to reduce the extent of oxidative damage caused by ethanol on the testes of rats.


Asunto(s)
Etanol/efectos adversos , Estrés Oxidativo/fisiología , Condicionamiento Físico Animal/efectos adversos , Testículo/metabolismo , Animales , Gatos/metabolismo , Cromatografía Líquida de Alta Presión , Ensayo de Inmunoadsorción Enzimática , Glutatión/metabolismo , Disulfuro de Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Peroxidación de Lípido/fisiología , Masculino , Oxidación-Reducción/efectos de los fármacos , Ratas , Ratas Endogámicas F344 , Superóxido Dismutasa/metabolismo , Testículo/efectos de los fármacos , Factores de Tiempo
14.
Indian J Physiol Pharmacol ; 42(3): 389-94, 1998 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9741654

RESUMEN

The present study elucidates the behavioral and toxic signs in rats following dermal application of sulphur mustard (SM). Graded doses of SM (0.10, 0.25, 0.50, 0.75 and 1.0 LD50) were topically applied to male Wister rats. The body weight as well as behavioral/toxic signs and symptoms were recorded at 1, 2, 3, and 4th day after application of SM. Sulphur mustard consistently decreased body weights of rats in a dose and time dependent manner with maximum decrease on 3rd day post treatment. Sedation and diarrhea were significant in response to doses of SM intoxication in rats. It is concluded that the body weight, sedation and diarrhea may be used as a reliable parameter in evaluating SM intoxication. It is also suggested that hydration and hypertonic saline must be used as a rescue agent within 1-3 days after exposure to SM.


Asunto(s)
Gas Mostaza/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Diarrea/inducido químicamente , Relación Dosis-Respuesta a Droga , Inflamación/inducido químicamente , Masculino , Piloerección/efectos de los fármacos , Ratas , Ratas Wistar , Salivación/efectos de los fármacos , Factores de Tiempo
15.
Artículo en Inglés | MEDLINE | ID: mdl-9608610

RESUMEN

1. This study examines the effects of exercise training and chronic ethanol consumption on cholinesterase activity and its relationship to lipid peroxidation in blood and brain regions of rat. 2. Exercise training (6.5 weeks) decreased acetylcholinesterase (AChE) activity significantly (64% of control) in hypothalamus and increased AChE activity in cerebral cortex (149% of control), whereas, malondialdehyde (MDA) levels increased in hypothalamus (129% of control) and decreased in cortex, striatum, and cerebellum (50%, 69% and 75% of control), respectively. 3. Chronic ethanol ingestion (2.0 gm/kg, p.o. for 6.5 weeks) significantly increased butyrylcholinesterase (BuChE) activity in plasma (136% of control) and decreased AChE activity in hypothalamus (63% of control), whereas, MDA levels increased in hypothalamus, cortex, and plasma (140%, 130% and 220% of control), respectively. 4. The combination significantly increased BuChE activity (173% of control) in plasma and decreased AChE activity (71% of control) in hypothalamus and (57% of control) in cerebellum, whereas, MDA levels increased in hypothalamus, cerebellum, medulla and plasma (134%, 128%, 140% and 309% of control), respectively. 5. Exercise training, chronic ethanol ingestion, and combination selectively inhibited hypothalamic AChE and the inhibition was correlated with increased lipid peroxidation (r = 0.11, 0.41 and 0.45) which may perturb hypothalamic function. The combination enhanced the peripheral stress response by increasing plasma BuChE activity and lipid peroxidation.


Asunto(s)
Depresores del Sistema Nervioso Central/farmacología , Colinesterasas/metabolismo , Etanol/farmacología , Peroxidación de Lípido/efectos de los fármacos , Condicionamiento Físico Animal , Animales , Encéfalo/metabolismo , Colinesterasas/sangre , Colinesterasas/efectos de los fármacos , Masculino , Ratas , Ratas Endogámicas F344
16.
Mol Cell Biochem ; 178(1-2): 127-33, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9546591

RESUMEN

This study was designed to investigate the cisplatin-induced alteration in renal antioxidant system and the nephroprotection with ebselen. Male Wistar rats were injected with (1) vehicle control; (2) cisplatin; (3) ebselen; and (4) cisplatin plus ebselen. Rats were sacrificed three days post-treatment and plasma as well as kidney were isolated and analyzed. Plasma creatinine increased 598% following cisplatin administration alone which decreased by 158% with ebselen pretreatment. Cisplatin-treated rats showed a depletion of renal glutathione (GSH) levels (52% of control), while cisplatin plus ebselen injected rats had GSH values close to the controls. Antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities decreased 38, 75 and 62% of control, respectively, and malondialdehyde (MDA) levels increased 174% of control following cisplatin administration, which were restored to control levels after ebselen treatment. The renal platinum level did not significantly change with ebselen pretreatment. This study suggests that the protection offered by ebselen against cisplatin-induced nephrotoxicity is partly related to the sparing of antioxidant system.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Antineoplásicos/toxicidad , Antioxidantes/farmacología , Azoles/farmacología , Cisplatino/toxicidad , Riñón/efectos de los fármacos , Compuestos de Organoselenio/farmacología , Animales , Catalasa/metabolismo , Creatinina/sangre , Glutatión/metabolismo , Disulfuro de Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Isoindoles , Riñón/metabolismo , Peróxidos Lipídicos/metabolismo , Masculino , Platino (Metal)/metabolismo , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo
17.
Pharmacol Toxicol ; 81(4): 173-9, 1997 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9353848

RESUMEN

This study was undertaken in order to determine the changes in auditory brainstem-evoked responses relationship with the changes in the levels of GSH, lipid peroxidation and antioxidant enzymes activity in cisplatin-induced ototoxicity and otoprotection by 4-methylthiobenzoic acid (MTBA). Male Wistar rats in different groups were treated as follows: 1) saline control; 2) cisplatin (16 mg/kg, intraperitoneally); 3) MTBA (250 mg/kg, intraperitoneally), and 4) cisplatin plus MTBA. Post-treatment auditory brainstem-evoked responses were performed after three days and the rats were sacrificed and cochleae harvested. The cochleae were analyzed for glutathione (GSH), antioxidant enzyme activity, and malondialdehyde levels. The cisplatin injected rats showed a threshold elevation of 31.9 +/- 16.0 dB above the pretreatment thresholds using click stimulus. Rats treated with MTBA plus cisplatin did not show significant elevation of hearing threshold. Cisplatin plus MTBA administration showed a higher levels of cochlear GSH (5.59 +/- 0.35 nmoles/mg protein) compared to cisplatin alone (4.46 +/- 0.13 nmoles/mg protein). Cisplatin treated rats showed a decrease in superoxide dismutase, catalase, glutathione peroxidase (GSH-peroxidase), and glutathione reductase (GSH-reductase) activities (57%, 83%, 78% and 58% of control). Cochlear superoxide dismutase, catalase and GSH-reductase activities and MDA levels were restored in the rats injected with cisplatin plus MTBA, compared to cisplatin alone. It is concluded that the protection conferred by MTBA against cisplatin ototoxicity is associated with sparing of the cochlear antioxidant system.


Asunto(s)
Antineoplásicos/toxicidad , Antioxidantes/farmacología , Umbral Auditivo/efectos de los fármacos , Benzoatos/farmacología , Cisplatino/toxicidad , Cóclea/enzimología , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Estimulación Acústica , Animales , Catalasa/metabolismo , Cóclea/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/análisis , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo
18.
J Appl Toxicol ; 17(5): 329-36, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9339746

RESUMEN

This study investigates the interactive effects of chronic ethanol ingestion and exercise training on the antioxidant system and lipid peroxidation in cortex, cerebellum, medulla, striatum and hypothalamus of the rat brain. Exercise training (6.5 weeks) significantly increased superoxide dismutase (SOD) activity in striatum, the region associated with motor activity, but decreased SOD activity in other brain regions. Catalase (CAT) activity decreased significantly in hypothalamus, the region associated with behavior, due to exercise. The training significantly increased glutathione peroxidase (GSH-Px) activity in brain regions studied with the exception of cerebellum. In addition, glutathione reductase (GR) activity increased in brain regions, with the exception of medulla. The training significantly decreased malondialdehyde (MDA) levels in all brain regions studied, which is due to training adaptation. Ethanol (20%) (2.0 g kg[-1], p.o. for 6.5 weeks) significantly decreased SOD activity in all regions except cortex, CAT activity in cortex, striatum and hypothalamus, GSH-Px activity in cerebellum and GR activity in medulla. Similarly, ethanol significantly decreased the GSH level in cortex, medulla and striatum and the GSH/GSSG ratio in medulla and cerebellum. Conversely, ethanol significantly augmented GR activity in cortex, cerebellum and striatum. When ethanol and exercise were combined, there was significantly increased SOD and CAT activity in striatum, GSH-Px activity in cortex, striatum and hypothalamus and GR activity in cortex and striatum. The GSH level was significantly depleted in cortex, striatum and medulla. Combining training and ethanol also decreased MDA levels in medulla and cerebellum. In conclusion, the sensitivity of specific brain regions in reaction to chronic ethanol ingestion or training is a function of variability in antioxidant system activity. Thus, exercise training protects specific brain regions against ethanol-induced oxidative injury.


Asunto(s)
Antioxidantes/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Depresores del Sistema Nervioso Central/toxicidad , Etanol/toxicidad , Peroxidación de Lípido/efectos de los fármacos , Condicionamiento Físico Animal/fisiología , Animales , Catalasa/análisis , Catalasa/metabolismo , Depresores del Sistema Nervioso Central/administración & dosificación , Etanol/administración & dosificación , Glutatión Peroxidasa/análisis , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/análisis , Glutatión Reductasa/metabolismo , Peroxidación de Lípido/fisiología , Masculino , Malondialdehído/análisis , Malondialdehído/metabolismo , Estrés Oxidativo/fisiología , Ratas , Ratas Endogámicas F344 , Superóxido Dismutasa/análisis , Superóxido Dismutasa/metabolismo
19.
Artículo en Inglés | MEDLINE | ID: mdl-9194147

RESUMEN

1. This study elucidates the interaction of acute exercise and single ethanol intake on cholinergic enzyme and its relationship to lipid peroxidation in the blood and brain regions of the rat. 2. Butyrylcholinesterase (BuChE) in plasma and acetylcholinesterase (AChE) in brain regions as well as lipid peroxidation (MDA) were assayed in 1) sedentary control rats; 2) after acute exercise (100% VO2max); 3) ethanol 20% (1.6 gm/kg, p.o.); 4) exercise and then ethanol 20% (1.6 gm/kg, p.o.). 3. Acute exercise significantly increased BuChE activity (155% of control) in plasma and decreased AChE activity (60% of control) in the corpus striatum with a significant increase in the striatal MDA level (254% of control). Ethanol significantly decreased AChE activity only in striatum (86% of control) with a significant increase in striatal MDA level (132% of control). 4. The combination of exercise and ethanol 20% (1.6 gm/kg, p.o.) significantly increased BuChE activity (123% of control) in plasma, and decreased AChE activity (76% of control) in striatum with significant increase in striatal MDA level (147% of control). 5. Acute exercise, single ethanol 20% (1.6 gm/kg, p.o.) intake and the combination selectively inhibited striatal AChE, and the inhibition was correlated with increased lipid peroxidation indicating perturbation of motor function. The combination reduced the peripheral stress response caused by exhaustive exercise.


Asunto(s)
Encéfalo/efectos de los fármacos , Colinesterasas/efectos de los fármacos , Etanol/farmacología , Peroxidación de Lípido/efectos de los fármacos , Condicionamiento Físico Animal/fisiología , Animales , Encéfalo/metabolismo , Colinesterasas/sangre , Masculino , Ratas , Ratas Endogámicas F344
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