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S M Somani

Publications and source records attributed to S M Somani.

At least 19 recordsLinked to original sources
PubMed2001

Dose response of carboplatin-induced hearing loss in rats: antioxidant defense system.

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.

Animals↗
PubMed2001

Carboplatin-induced oxidative stress in rat cochlea.

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.

Animals↗
PubMed2001

Chronic ethanol and nicotine interaction on rat tissue antioxidant defense system.

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.

Animals↗
PubMed2000

Delayed effects of pyridostigmine and exercise training on acetylcholinesterase and muscle tension in mouse lower extremity.

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.

Acetylcholinesterase↗
PubMed2000

Dose-dependent protection by lipoic acid against cisplatin-induced nephrotoxicity in rats: antioxidant defense system.

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.

Animals↗
PubMed1999

Dose- and time-dependent effects of ethanol on plasma antioxidant system in rat.

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.

Animals↗
PubMed1999

Dose dependent protection by lipoic acid against cisplatin-induced ototoxicity in rats: antioxidant defense system.

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.

Animals↗
PubMed1999

Dose response of ethanol ingestion on antioxidant defense system in rat brain subcellular fractions.

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.

Animals↗
PubMed1998

Effect of exercise training and chronic ethanol ingestion on cholinesterase activity and lipid peroxidation in blood and brain regions of rat.

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.

Animals↗
PubMed1998

Protection by ebselen against cisplatin-induced nephrotoxicity: antioxidant system.

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.

Animals↗
PubMed1998

Dose response of sulphur mustard: behavioral and toxic signs in rats.

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.

Animals↗
PubMed1997

Influence of exercise and ethanol on cholinesterase activity and lipid peroxidation in blood and brain regions of rat.

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.

Animals↗
PubMed1997

Protection by 4-methylthiobenzoic acid against cisplatin-induced ototoxicity: antioxidant system.

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.

Acoustic Stimulation↗
PubMed1996

4-methylthiobenzoic acid protection against cisplatin nephrotoxicity: antioxidant system.

This study investigates the changes in renal antioxidant system after cisplatin administration and the nephroprotection with 4-methylthiobenzoic acid (MTBA). Male Wistar rats were injected with (1) vehicle control, (2) cisplatin, (3) MTBA, and (4) cisplatin plus MTBA. Rats were euthenized 3 days post-treatment and kidney was isolated and analyzed for platinum concentration, malondialdehyde (MDA), glutathione (GSH and GSSG), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Plasma creatinine increased 508% following cisplatin administration alone, which decreased to 189% with MTBA. Cisplatin-treated rats showed a depletion of renal GSH levels (53%), while cisplatin plus MTBA-injected rats had GSH values close to those of the controls. SOD, CAT, and GSH-Px activities decreased 36, 29, and 38%, respectively, and MDA levels increased 212% following cisplatin administration, which were restored to control levels after MTBA treatment. The renal platinum level depleted significantly with MTBA treatment. The data suggest that cisplatin nephrotoxicity is mediated by depletion in GSH concentration and by impaired activities of SOD, CAT, and GSH-Px, increased lipid peroxidation, and plasma creatinine levels. The protection offered by MTBA against cisplatin nephrotoxicity is related to the reduction in plasma creatinine levels, prevention of GSH depletion and lipid peroxidation, and restoring antioxidant enzyme activity in the kidneys of rats.

Animals↗
PubMed1996

Exercise training alters kinetics of antioxidant enzymes in rat tissues.

Michaelis-Menten constant (Km) and maximum velocity (Vmax) of catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) in various tissues of exercise-trained old rats were compared with the age matched sedentary control. Exercise training increased the maximum velocity (Vmax) for CAT in the brain (350%), liver (33%), lung (34%), muscle (25%) and testes (21%); for GSH-Px (using t-butyl hydroperoxide as a substrate) in the liver (22%), lung (25%), and testes (52%); for GSH-Px (using GSH as a cosubstrate) in the brain (64%) and liver (100%), and for GR in testes (50%). This increase in Vmax indicates the potential activation of these enzymes in the specific tissues. Exercise training differentially altered the affinities of enzyme (Km) for CAT, GSH-Px and GR to their substrates. These studies suggest that exercise training provided a beneficial role by activation of antioxidant enzymes in specific tissues of aged rats. Thus, exercise training aids in coping with oxidative stress in old age.

Animals↗
PubMed1996

Comparative effects of exercise training on transcription of antioxidant enzyme and the activity in old rat heart.

An increase in antioxidant enzyme activity after acute exercise and exercise training have been reported by many investigators including our laboratory. This study was undertaken in order to determine whether an increase in activity of superoxide dismutase (MnSOD and CuZnSOD), catalase (CAT) and glutathione peroxidase (GSH-Px) during exercise training was associated with the increased levels of respective mRNAs. Male Fisher-344 rats (age 77 weeks) were given exercise training for 9 weeks on the treadmill. Enzyme activity and mRNA's were measured in the heart tissue 23 hr after stopping exercise training. The heart tissues of exercised and sedentary control rats were used to isolate mRNAs encoding MnSOD, CuZnSOD, CAT and GSH-Px by northern blotting experiments. The intensities of mRNA bands were measured by densitometric scanning of the autoradiograms. Northern blot for tubulin was used to normalize the respective intensities. Compared to sedentary controls, the level of mRNAs of enzymes MnSOD, CAT and GSH-Px were found to increase by 126 +/- 5, 133 +/- 6, and 138 +/- 5 percent of sedentary control (mean +/- SEM) respectively, due to exercise training. Corresponding values for these enzyme activity were 153 +/- 19%, 255 +/- 7%, 133 +/- 2% of sedentary control. These results suggest that post-translational modification of these enzyme activity increased in response to exercise training more than increased transcription in aged rats.

Animals↗
PubMed1995

Mechanism of protection by diethyldithiocarbamate against cisplatin ototoxicity: antioxidant system.

This investigation was undertaken to explain the possible, mechanism(s) of protection by diethyldithiocarbamate (DDTC) against cisplatin ototoxicity. Male Wistar rats (250-275 g) underwent pretreatment auditory brain stem-evoked responses (ABRs). The different groups of rats were injected as follows: (1) cisplatin (16 mg/kg i.p.), (2) cisplatin plus DDTC (16 mg/kg i.p. + 600 mg/kg, s.c.), and (3) control rats. Post-treatment ABRs were performed after 3 days and the rats were euthanized and cochleae were harvested. The cochleae were analyzed for glutathione (GSH) and oxidized glutathione, by HPLC, and for the activities of the antioxidant enzymes, and malondialdehyde levels, by spectrophotometry. The cisplatin-injected rats showed a threshold elevation of 36 +/- 3.05 dB above the pretreatment thresholds using click stimulus. Rats treated with cisplatin and then DDTC did not show a significant elevation of hearing threshold. DDTC-mediated protection was associated with higher levels of GSH (0.81 +/- 0.11 nmol/mg tissue), compared to 0.45 +/- 0.02 nmol/mg tissue following administration of cisplatin alone. Administration of cisplatin + DDTC restored the cochlear GSH-Px activity to control level. Cisplatin-treated rats were found to have decreased GSH-Px activity (75% of control). Cochlear SOD and CAT activities and MDA levels showed a decreasing trend in the animals injected with cisplatin + DDTC, compared to cisplatin-alone-treated rats. These data suggest that the protection conferred by DDTC against cisplatin ototoxicity is associated with sparing of the cochlear GSH/GSH-Px.

Animals↗