Lindane Administration Research Articles

Effect of Lindane (δ- isomer) on Serum cholesterol and Liver enzyme markers in mice (Mus musculus)

In the present study, we investigate the serum cholesterol level and the liver enzymes (alkaline phosphatase, alanine transaminase, and aspartate aminotransferase) in mice. Lindane (δ- isomer), 100mg/kg body weight, injected subcutaneously for 30 days. Our present study found that after 30 days of lindane administration, after sacrificing the mice, a significant increase in serum cholesterol levels observed. Alkaline phosphatase levels significantly decreased, whereas the alanine transaminase and aspartate aminotransferase levels significantly increased.

Experimental chronic sleep fragmentation alters seizure susceptibility and brain levels of interleukins 1β and 6.

Brain hyperexcitability in sleep apnea is believed to be provoked by hypoxemia, but sleep fragmentation can also play a significant role. Sleep fragmentation can trigger inflammatory mechanisms. The aim of this research was to investigate the effects of chronic sleep fragmentation on seizure susceptibility and brain cytokine profile. Chronic sleep fragmentation in male rats with implanted EEG electrodes was achieved by the treadmill method. Rats were randomized to: treadmill control (TC); activity control (AC) and sleep fragmentation (SF) group. Convulsive behavior was assessed 14 days later by seizure incidence, latency time and seizure severity during 30 min following lindane administration. The number and duration of EEG ictal periods were determined. Levels of IL-1β and IL-6 were measured in the animals' serum and brain structures (hippocampus, thalamus and cerebral cortex), in separate rat cohort that underwent the same fragmentation protocol except lindane administration. Incidence and severity of seizures were significantly increased, while latency was significantly decreased in SF+L compared with TC+L group. Seizure latency was also significantly decreased in SF+L compared to AC+L group. The number and duration of ictal periods were increased in the SF+L compared to the AC+L group. IL-1β was significantly increased in the thalamus, cortex and hippocampus in the SF compared to the AC and TC groups. IL-6 was statistically higher only in the cortex of SF animals, while in the thalamic or hippocampal tissue, no difference was observed between the groups. It could be concluded that fourteen-day sleep fragmentation increases seizure susceptibility in rats and modulates brain production of IL-1β and IL-6. Brain hyperexcitability in sleep apnea is believed to be provoked by hypoxemia, but sleep fragmentation can also play a significant role. Sleep fragmentation can trigger inflammatory mechanisms. The aim of this research was to investigate the effects of chronic sleep fragmentation on seizure susceptibility and brain cytokine profile. Chronic sleep fragmentation in male rats with implanted EEG electrodes was achieved by the treadmill method. Rats were randomized to: treadmill control (TC); activity control (AC) and sleep fragmentation (SF) group. Convulsive behavior was assessed 14 days later by seizure incidence, latency time and seizure severity during 30 min following lindane administration. The number and duration of EEG ictal periods were determined. Levels of IL-1β and IL-6 were measured in the animals’ serum and brain structures (hippocampus, thalamus and cerebral cortex), in separate rat cohort that underwent the same fragmentation protocol except lindane administration. Incidence and severity of seizures were significantly increased, while latency was significantly decreased in SF+L compared with TC+L group. Seizure latency was also significantly decreased in SF+L compared to AC+L group. The number and duration of ictal periods were increased in the SF+L compared to the AC+L group. IL-1β was significantly increased in the thalamus, cortex and hippocampus in the SF compared to the AC and TC groups. IL-6 was statistically higher only in the cortex of SF animals, while in the thalamic or hippocampal tissue, no difference was observed between the groups. It could be concluded that fourteen-day sleep fragmentation increases seizure susceptibility in rats and modulates brain production of IL-1β and IL-6.

Folic acid supplementation alleviates behavioral manifestations of lindane-induced seizures

Lindane is a scabicide and pesticide that can exert neurotoxic effects such as tonic and clonic seizures that are refractory to many antiepileptic drugs. Folic acid stands out as a potential substance worth testing for its neuroprotective and in certain experimental models anticonvulsive effects. The aim of the present study was to examine the potential therapeutic value of folic acid supplementation on the behavioral characteristics of lindane-induced seizures. Adult male Wistar rats were divided into the following groups: Controls: dimethyl sulfoxide-injected (C1), saline-treated (C2); lindane (4 mg/ kg; 6 mg/kg; 8 mg/kg; L4; L6; L8, respectively); folic acid 15 mg/kg (F) and F administered 30 min prior to L4, L6, or L8 (L4F; L6F; L8F, respectively). Convulsive behavior was assessed by the incidence of seizures, seizure latency and seizure severity. Lindane administration has shown a tendency of proportional increase in seizure incidence, decrease in seizure latency and increase in seizure intensity. Pretreatment with folic acid significantly prolonged the latency period and decreased the frequency of grade 4 seizures in the L8F group when compared to the L8 group. We concluded that folic acid alleviates the behavioral manifestations of lindane-induced seizures and that it can be applied as a potential adjuvant in lindane-poisoned patients; however, further research is still needed. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 175032]

Study of pathological lesions in rats after the experimental administration of Lindane

In this experimental study, the lesions that are caused from the chemical substance Lindane were studied. Sixteen rats were used as experimental animals. The substance was orally administered, with food, to 10 rats (5 females and 5 males) in a dose of 8,2 mg/kg b.w./3 days during the first 10 days and in a dose of the 33 mg/kg b.w./ 2 days during the following 40 days. The remaining 6 rats (4 females and 2 males) were used as controls. The mainly clinical symptoms which were observed in the experimental animals, in the end of the experimentation, were anorexia, lethargy, hypothermia and muscular rigor. All the rats were sacrificed 5 days after the administration of the last dose of the substance and they were autopsied. In the macroscopical examination oedema and vascular hyperhaemia were observed in the brain. In the histological examination spongiosis of the white matter of the brain, interstitial pneumonia, oedema and loss of the cross striation of the cardiac muscle cells, coagulative necrosis of individual groups of hepatic cells and degeneration of the epithelial cells of the urinary tubules were detected. In conclusion, when Lindane is administered in subtoxical doses for a long period of time it is possible to cause damages to the organism of the experimental animals, which are located mainly in the brain and secondary in the liver, the kidneys and the other organs.

Effect of treatment of cow’s urine “Gomutra” and antioxidants in alleviating the lindane-induced oxidative stress in kidney of Swiss mice (Mus musculus)

The study aimed to evaluate the effect of cow urine and combination of antioxidants against lindane induced oxidative stress in Swiss mice. Male healthy mice, 8-10 weeks old, weighing 30 ± 5 g were randomly selected and divided into eight groups, namely, control (C); lindane (L); antioxidant (A), antioxidant+lindane (A+L), cow urine (U), cow urine+lindane (U+L), cow urine+antioxidants (U+A) and cow urine+antioxidants+lindane (U+A+L). Group C animals were administered only the vehicle (olive oil); doses selected for other treatments were: lindane: 40 mg/kg b.w.; antioxidants: 125 mg/kg b.w. (vitamin C: 50 mg/kg b.w., vitamin E: 50 mg/kg b.w., α-lipoic acid: 25 mg/kg b.w.) and cow urine: 0.25 ml/kg b.w. In group A+L and U+L antioxidants and cow urine were administered 1 h prior to lindane administration and in group U+A and U+A+L cow urine was administered 10 min before antioxidants. All treatments were administered orally continuously for 60 days. Lindane treated group showed increased lipid peroxidation, whereas glutathione, glutathione peroxidase, superoxide dismutase, catalase, protein and endogenous levels of vitamin C and E were significantly decreased compared to control. Administration of cow urine and antioxidants alleviated the levels of these biochemical parameters.

To study the oxidative stress induced by lindane in epileptic rats brains and their modulation by Neurosteroids

Background: Lindane is pesticide has been shown to affect the nervous system adversely. Previous work has shown that lindane is proconvulsant and neurosteroids (NS) has been shown to be neuroprotective against lindane-induced convulsions. As the mechanisms of lindane in epileptogenesis is not completely understood. The present study was designed to investigate the oxidative stress parameters of lindane toxicity in epileptogenesis and their modulation by NS like allopregnanolone (AP), and 4ʹ-chlorodiazepam (4ʹ-CD) in pentylenetetrazole (PTZ) kindling methods. Methods: Kindling was induced by injecting PTZ (30 mg/kg; s.c.) on alternate days i.e., 3 times in a week. Lindane was also administered (15 mg/kg p.o) on alternate days for 6 weeks. AP (2.5 mg/kg, intaperitoneal [i.p.]) and 4ʹ-CD (0.5 mg/kg, i.p.) single dose was given in kindled rats before lindane. Results: Following per oral administration of lindane for 6 weeks produced significant oxidative stress in epileptic brain. There was an increase in brain malondialdehyde (MDA) level and decrease in reduced glutathione (GSH) levels. AP (2.5 mg/kg, i.p.) and 4ʹ-CD (0.5 mg/kg, i.p.) single dose administration were not able to reverse the effect of chronic exposure of lindane. Conclusion: The result of the present study provides evidence that oxidative stress produced in the brain after chronic exposure of lindane may be the mechanism of epileptogenesis. Though NS have been shown to be neuroprotective, but they failed to reverse chronic oxidative stress produced by lindane. Further studies are required to demonstrate interaction of NS with lindane in oxidative stress.

24. Aminooxyacetate, an inhibitor of H2S production, potentiates lindane-induced convulsions in rats

Purpose: H 2 S is a gaseous molecule recently recognized as endogenously produced neurotransmitter with different, still not well known, physiological and pathological roles. Cystathionine- β -synthase (CBS) is a major enzyme responsible for H 2 S production in the brain. The aim of this study was to investigate the effects of aminooxyacetate, potent CBS inhibitor, on convulsions induced by lindane in rats. Methods: Adult male Wistar albino rats were intraperitoneally (i.p.) treated with lindane 4 mg/kg and observed for convulsive behavioral manifestations during next 30 min. Aminooxyacetate (0.25 mmol/kg) or saline were injected 30 min prior to lindane administration. Seizure behavior was assessed by seizure incidence, latency time to first seizure onset and its severity assessed by descriptive scale with 4 grades. Results: Seizure incidence was higher in rats treated with aminooxyacetate prior to lindane, but the difference were not statistically significant comparing with those treated only with lindane. However, administration of aminooxyacetate significantly decreased the latency time to first seizure and significantly augmented severity of lindane-induced seizures. Conclusion: These results showed that aminooxyacetate, an inhibitor of H 2 S production, potentiated convulsive activity of lindane in rats.

Quercetin attenuates lindane induced oxidative stress in wistar rats

A wide number of pesticides, including highly persistent organochlorine compounds, such as lindane (γ-Hexachlorocyclohexane), have deteriorative effect on fauna and flora by inducing oxidative stress. Lindane induces cell damage by producing free radicals and reactive oxygen species. Quercetin, a dietary flavonoid, is ubiquitous in fruits and vegetables and plays an important role in human health by virtue of its antioxidant function. In this study the flavonoid quercetin was used to investigate its antioxidative effect against lindane induced oxidative stress in rats. The level of lipid peroxidation, reduced glutathione (GSH) were analysed in addition to the antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione-s-transferase (GST) activities in the liver and kidney tissue. Levels of hepatic marker enzymes in serum like Aspartate transaminase (AST), Alanine transaminase (ALT), Alkaline phosphatase (ALP) and Lactate dehydrogenase (LDH) and renal markers like serum creatinine and serum urea were estimated. Administration of Lindane induced histopathological alterations and increased levels of serum hepatic and renal markers and malondialdehyde (MDA) with a significant decrease in GSH content and CAT, SOD, GPx and GST activities. Cotreatment of quercetin along with lindane significantly decreased the lindane induced alteration in histology, serum hepatic and renal markers and MDA and also improved the cellular antioxidant status. The results show that Quercetin ameliorates Lindane induced oxidative stress in liver and kidney. The quercetin exhibited chemopreventive effect when administered along with lindane.

Dichlorvos and lindane induced oxidative stress in rat brain: Protective effects of ginger

Background:Dichlorvos and lindane pesticide causes toxicity in animals including humans. Ginger (Zingiber officinale) is widely used as a culinary medicine in the Ayurvedic system of medicine, possessing a number of pharmacological properties.Objective:This study was designed to assess ameliorating effects of ginger juice in dichlorvos and lindane induced neurotoxicity in wistar rats.Materials and Methods:Dichlorvos (8.8 mg/kg bw) and lindane (8.8 mg/kg bw) were orally administered alone as well as in combination to adult male and female wistar rats for 14 days followed by the post-treatment of ginger juice (100 mg/kg bw) for 14 days. Lipid peroxidation (LPO), reduced glutathione (GSH), and activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR), quinine reductase (QR), and protein level were measured to evaluate the toxicity of these pesticides in brain.Results:Dichlorvos and lindane administration alone and in combination increased LPO and decreased the GSH level, SOD, CAT, GPx, GST, GR, QR activity, and protein. Oxidative stress due to abnormal production of reactive oxygen species (ROS) is believed to be involved in the toxicities induced by these pesticides. Post-treatment of ginger juice decreased LPO and increased the level of GSH, SOD, CAT, GPx, GST, GR, QR activity and protein in the brain of rats.Conclusions:The results indicated that dichlorovos and lindane induced tissue damage was ameliorated by ginger juice.

290 The role of tetraspanins in antigen presentation to CD4+ T cells via exosomes

This study examines possible synergistic effects of lindane and ethanol on inducing liver injury and serum fatty acid derangement in adult male Wistar rats. When administered together, ethanol and lindane-induced even more pronounced increase of alanine aminotransferase (165 ± 10 U/L) and gamma-glutamyltranspeptidase activity (10.3 ± 0.6 U/L) than after isolated administration of either substance. In addition, separate administration of lindane and ethanol was followed by a significant decrease of linoleic acid level in the serum (301 ± 38 mg/L, 276 ± 35 mg/L vs. 416 ± 48 mg/L). However, when ethanol administration was followed by lindane injection, serum linoleic acid was at the similar level found in the control group (516 ± 62 mg/L). Ethanol-treated rats that received lindane 30 min after ethanol administration have shown a marked increase of palmitic (421 ± 27 mg/L) and linolic acid level (43 ± 5 mg/L) in comparison with rats that have been treated only with ethanol (316 ± 26 mg/L for palmitic and 32 ± 2 mg/L for linolic acid) or lindane (295 ± 26 mg/L for palmitic and 301 ± 38 mg/L for linolic acid). Linolic acid level was significantly greater in comparison with control group (29 ± 1 mg/L). In conclusion, this study found enough evidence to support the hypothesis that acute ethanol intoxication potentiates lindane-induced liver injury and enhances lipid derangement.

Oxidative stress in liver and red blood cells in acute lindane toxicity in rats

The aim of our study was to determine the role and dynamics of oxidative and nitrosative stress, as well as superoxide dismutase (SOD) and catalase activity in the hepatocytes and erythrocytes in early phase of acute lindane intoxication. Male Wistar rats were divided into groups: control, dimethylsulfoxide and lindane-treated groups (L, 8 mg/kg, intraperitoneally). Animals were sacrificed 0.5 and 4 hours after treatment (L(0.5) and L(4) groups, respectively). Oxidative and nitrosative stress parameters and antioxidant enzymes were determined spectrophotometrically. Liver and plasma thiobarbituric acid reactive substances (TBARS) concentration were significantly increased 0.5 after lindane administration (p < .01), with subsequent additional rise within 4 hours (p < .01), while plasma nitrite + nitrate level was significantly higher only 4 hours after lindane treatment. Total liver SOD activity was significantly increased in L(4) group in comparison with control group (p < .01). In conclusion, oxidative and nitrosative stress play an important role in early phase of acute lindane hepatotoxicity. Antioxidant capacity of hepatocytes is partly increased, due to an adaptive increase in SOD activity.

Influence of NR2B-Selective NMDA Antagonist on Lindane-Induced Seizures in Rats

Ifenprodil is a novel NMDA receptor antagonist that selectively inhibits receptors containing the NR2B subunit. Lindane, a widely used pesticide and scabicide, evokes seizures mainly through the blockade of the γ-aminobutyric acid type A receptor complex. The aim of this study was to determine the effects of ifenprodil on the behavioral and electroencephalographic (EEG) manifestations of seizures in lindane-treated rats. Adult male Wistar rats with three electrodes implanted into the skull were treated intraperitoneally (i.p.) with lindane 8 mg/kg and observed for seizure behavior and EEG during the next 30 min. Seizure behavior was assessed by incidence, severity (determined by a descriptive rating scale ranging from 0 to 4) and duration of latency. Increasing doses of ifenprodil (5, 10, 20 mg/kg, i.p.) or vehicle were injected 30 min prior to lindane administration. Ifenprodil decreased the incidence and severity of lindane seizures and prolonged the latency to seizures in a dose-dependent manner. 20 mg/kg of ifenprodil significantly de- creased the incidence (p < 0.05) and severity (p < 0.05) of seizures when compared to the vehicle treatment. Latency to seizures was significantly prolonged by 10 and 20 mg/kg of ifenprodil. The estimated ED₅₀ value of ifenprodil was 15.53 (5.48–15.20) mg/kg. The lindane-induced bursts of spiking activity in EEG were not completely suppressed by the applied doses of ifenprodil. These results indicate that ifenprodil alleviates behavioral seizures and modifies EEG characteristics of lindane seizures in rats, thus showing the involvement of NMDA receptors containing the NR2B subunit in the mechanisms of lindane convulsions.

The correlation between lipid peroxidation in different brain regions and the severity of lindane-induced seizures in rats

The aim of this study was to investigate the dynamics of lipid peroxidation and the possible correlation between lipid peroxidation in different brain regions and behavioral manifestations in lindane-induced seizures in rats. Male Wistar rats were divided into the following groups: 1. control, saline-treated group; 2. dimethylsulfoxide (DMSO)-treated group; 3. lindane-treated group (8 mg/kg), intraperitoneally. Animals were sacrificed 0.5 or 4 h after treatment and the malondialdehyde level and superoxide dismutase (SOD) activity were determined in various brain regions spectrophotometrically. Behavioral changes were classified according to the descriptive scale (0--no response, 1--head nodding, lower jaw twitching; 2--myoclonic body jerks, bilateral forelimb clonus with full rearing; 3--progression to generalized clonic convulsions followed by tonic extension of fore- and hind limbs and tail; 4--status epilepticus). A significant rise in the malondialdehyde level was detected in the cerebral cortex, hippocampus, and thalamus of lindane-treated animals 0.5 and 4 h after administration (P < 0.05). SOD activity (total and mitochondrial) was significantly decreased in the hippocampus and the cortex of lindane-treated animals at both time points (P < 0.05). An initial fall in SOD activity was detected in the thalamus 4 h after lindane administration (P < 0.05). A positive correlation between seizure severity and the malondialdehyde level was found in the hippocampus at both time points (P < 0.01). These results suggest that lipid peroxidation may contribute to the neurotoxic effects of lindane in early acute lindane intoxication and that behavioral manifestations correlate with lipid peroxidation in the hippocampus of lindane-treated rats.

14. Effect of ethanol on epileptiform activity induced by nickel on Retzius nerve cells of the leech

groups: (1) control, saline-treated group (n = 16), (2) dimethylsulfoxide-treated group (n = 16), (3) group that received lindane, dissolved in dimethylsulfoxide, in a dose of 8 mg/kg intraperitoneally (n = 16). Eight animals from each group were sacrificed 0.5 and 4 h after treatment and brain samples were prepared for further analysis. Acetylcholinesterase activity (mitochondrial and synaptosomal fraction) was determined in cerebral cortex, thalamus, hippocampus and nc. caudatus spectrophotometrically. Results: A significant rise in mitochondrial acetylcholinesterase activity was detected in cortex and nucleus caudatus of lindane-treated animals 0.5 h after administration (p < 0.05). This rise was sustained in nucleus caudatus within 4 h after treatment (p < 0.05). In contrast, activity of synaptosomal acetylcholinesterase fraction was significantly increased only in thalamus 4 h after lindane administration (p < 0.05). Conclusion: An increase in acetylcholinesterase activity may be involved in mediating acute neurotoxic effects of lindane, at least in some brain structures in rats.

Protective effects of dietary ginger (Zingiber officinales Rosc.) on lindane-induced oxidative stress in rats.

The protective effect of dietary feeding of Zingiber officinales Rosc. (ginger) against lindane-induced oxidative stress was investigated in male albino rats. Oxidative stress was monitored by estimating the extent of lipid peroxidation, activities of the oxygen free radical (OFR) scavenging enzymes superoxide dismutase (SOD) and catalase (CAT) and the status of the glutathione redox cycle antioxidants. Lindane administration (30 mg/kg bw orally for 4 weeks) was associated with enhanced lipid peroxidation and compromised antioxidant defenses in rats fed a normal diet. Concomitant dietary feeding of ginger (1%w/w) significantly attenuated lindane-induced lipid peroxidation, accompanied by modulation of OFR scavenging enzymes as well as reduced glutathione (GSH) and the GSH dependent enzymes glutathione peroxidase (Gpx), glutathione reductase (GR) and glutathione-S-transferase (GST) in these rats. These findings suggest that a diet containing naturally occurring compounds is effective in exerting protective effects by modulating oxidative stress.

Effect of acute lindane and alcohol intoxication on serum concentration of enzymes and fatty acids in rats

This study examines possible synergistic effects of lindane and ethanol on inducing liver injury and serum fatty acid derangement in adult male Wistar rats. When administered together, ethanol and lindane-induced even more pronounced increase of alanine aminotransferase (165±10U/L) and gamma-glutamyltranspeptidase activity (10.3±0.6U/L) than after isolated administration of either substance. In addition, separate administration of lindane and ethanol was followed by a significant decrease of linoleic acid level in the serum (301±38mg/L, 276±35mg/L vs. 416±48mg/L). However, when ethanol administration was followed by lindane injection, serum linoleic acid was at the similar level found in the control group (516±62mg/L). Ethanol-treated rats that received lindane 30min after ethanol administration have shown a marked increase of palmitic (421±27mg/L) and linolic acid level (43±5mg/L) in comparison with rats that have been treated only with ethanol (316±26mg/L for palmitic and 32±2mg/L for linolic acid) or lindane (295±26mg/L for palmitic and 301±38mg/L for linolic acid). Linolic acid level was significantly greater in comparison with control group (29±1mg/L). In conclusion, this study found enough evidence to support the hypothesis that acute ethanol intoxication potentiates lindane-induced liver injury and enhances lipid derangement.

Single exposure to low dose of lindane causes transient decrease in testicular steroidogenesis in adult male Wistar rats

Substantial evidence has piled up portending the adverse effects of environmental toxicants on male reproduction. Lindane, an organochlorine pesticide, has been reported to perturb testicular functions and hence fertility. To get more insight into the mechanism(s) involved in gonadal effect(s) of lindane, we sought to investigate whether treatment with lindane at a low dose would alter the levels of steroidogenic acute regulatory protein (StAR), androgen binding protein (ABP) and activities of steroidogenic enzymes (3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase) in adult rat. Furthermore, the levels of H 2O 2 were monitored to delineate the possible role of H 2O 2 in mediating the testicular effects of lindane. Animals used for experimentation were divided into six groups and four animals were maintained in each group. Animals were administered with a single dose of lindane (5 mg/kg body weight) and terminated at specific post-treatment intervals (0 h, 3 h, 6 h, 12 h, 24 h and 72 h) to analyze the early testicular response. Administration of lindane resulted in a sequential reduction in the levels of StAR and the activities of steroidogenic enzymes with a parallel increase in the levels of H 2O 2. These changes elicited by lindane were significant at 12 h and 24 h post-treatment. In case of ABP, a significant decline in the level was found at 12 h after treatment. These findings demonstrate transient inhibitory effects of lindane on testicular steroidogenesis and the possible role of H 2O 2 in mediating these effects.

Lindane alters the levels of HSP70 and clusterin in adult rat testis

Lindane, an organochlorine pesticide, has been reported to induce reproductive abnormalities in male rats and induction of stress is considered to play an important role in the toxicity of lindane. To get more insight into the mechanism(s) involved in gonadal effect(s) of lindane, we sought to investigate whether treatment with lindane would alter the levels of stress proteins (heat shock proteins and clusterin) and change oxidative stress-related parameters (antioxidant enzymes and lipid peroxidation) in the testis of adult male rats. Animals used for experimentation were divided into six groups and four animals were maintained in each group. Animals were administered with a single dose of lindane (5 mg/kg body weight) and terminated at specific post-treatment intervals (0, 3, 6, 12, 24 and 72 h) to analyze the early stress response. Administration of lindane resulted in a sequential reduction in the activities of catalase and superoxide dismutase (SOD) with concomitant increase in the levels of lipid peroxidation. These changes elicited by lindane were significant between 6 and 24 h post-treatment. In case of heat shock protein, the level of the constitutive HSP70 remained constant at all post-treatment intervals. However, a significant induction in the level of inducible HSP70 was observed between 6 and 24 h post-treatment. Similarly, the levels of secretory clusterin (sCLU) was found be significantly elevated at 12 and 24 h after treatment. These findings indicate a transitory state of stress induced by lindane in rat testis accompanied by an alteration in the levels of stress proteins, which could be a part of protective mechanism mounted to reduce cellular damage.

Induction of oxidative stress by lindane in epididymis of adult male rats

Lindane, an organochlorine pesticide, has been reported to induce reproductive abnormalities in male rats. The mechanism of action of lindane on male reproductive system remains unclear. In the present study we have sought to investigate the effect of lindane on antioxidant parameters and sialic acid levels of caput, corpus and cauda epididymis of adult male rats. Lindane (1, 5, and 50 mg/kg per day) was administered orally to adult male rats for 45 days. The animals were killed using anaesthic ether on the day following the last treatment. The body weight of the animals did not show significant change. However, the weights of caput, corpus and cauda epididymis decreased in lindane treated animals. Administration of lindane caused decrease in epididymal sperm count and motility. Sialic acid levels in the epididymis decreased significantly at 5 and 50 mg/kg dosage of lindane treatment. Significant decline in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase along with increase in hydrogen peroxide generation and lipid peroxidation were observed in lindane treated animals. In conclusion, lindane induces oxidative stress by decreasing the activities of antioxidant enzymes and sialic acid levels in the epididymis thereby causing impaired sperm function.

Administration of Xenobiotics With Anti-estrogenic Effects Results in mRNA Induction of Adult Male-Specific Cytochrome P450 Isozymes in the Livers of Adult Female Rats

Cytochrome P450 (CYP) catalyzes the oxidation of many endogenous and xenobiotic compounds. The expression of CYP isozymes are modulated by endogenous hormones and xenobiotics. We found that, although CYP2C11 and CYP3A2 are adult male-specific isozymes, they are also expressed in prepubertal female Sprague Dawley (SD) rats. However, the mRNA levels for these isozymes in prepubertal female SD rats decreased over time and became undetectable at 7 weeks of age. On the other hand, ovariectomy, administration of ICI182780, a specific estrogen antagonist, or administration of lindane, which is a widely used pesticide with anti-estrogenic effects, induced these adult male-specific CYP mRNAs in adult female SD rats. These results suggest that estrogen is involved in suppression of both CYP2C11 and CYP3A2 in adult female rats. The expression of these CYP isozymes in female rats, therefore, is affected by sexual maturity and by disrupting adult female hormonal homeostasis. We also performed a field survey to examine whether the induction of CYP2C11 or CYP3A2 differs between adult female roof rats in rural and metropolitan districts. RT-PCR showed that the mRNAs for CYP2C11 and CYP3A2 were expressed in half of the adult female roof rats captured in Osaka (as a metropolitan area district) but not in those captured in Hokkaido (as a rural district). Thus, induction of the adult male-specific CYP isozymes in adult female roof rats captured in Osaka might be caused by consumption of xenobiotics with anti-estrogenic effects.