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Objective:To explore the genotoxic potential and histopathological changes induced in liver,kidney,testis,brain and heart after using the antibiotic drug amoxicillin/clavulanic acid (4∶1).Methods:The study included chromosomal aberration analysis in bone-marrow and mouse spermatocytes,induction of sperm morphological abnormalities and histopathological changes in different body organs.The drug was administrated orally at a dose of 81 mg/kg body weight twice daily (Total =162 mg/kg/day) for various periods of time equivalent to 625 mg/men (twice daily).Results:The results revealed non-significant chromosomal aberrations induced after treatment with amoxicillin/clavulanic acid (AC) in both bone marrow and mouse spermatocytes after 7 and 10 days treatment.On the other hand,statistically significant percentages of sperm morphological abnormalities were recorded.Such percentage reached 8.10 ± 0.55,9.86 ± 0.63 and 12.12 ± 0.58 at the three time intervals tested (7,14and 35 days after the 1st treatment respectively) (treatment performed for 5 successive days) compared with 2.78 ± 0.48 for the control.The results also revealed histopathological changes in different body organs after AC treatment which increased with the prolongation of the period of therapy.Congestion of central vain,liver hemorrhage and hydropic changes in hepatocytes were noticed in the liver.Degenerative changes were found in kidney glomerulus and tubules while testis showed atrophy of seminiferous tubules,and reduction of spermatogenesis.AC also induced neurotoxicity and altered brain neurotransmitter levels.Hemorrhage in the myocardium,disruption of cardiac muscle fibers and pyknotic nuclei in cardiomyocytes were recorded as side effects of AC in heart tissue.Contusions:The results concluded that AC treatment induced sperm morphological abnormalities and histopathological changes in different body organs.Clinicians must be aware of such results while describing the drug.
ABSTRACT
Objective To explore the genotoxic potential and histopathological changes induced in liver, kidney, testis, brain and heart after using the antibiotic drug amoxicillin/clavulanic acid (4:1). Methods The study included chromosomal aberration analysis in bone-marrow and mouse spermatocytes, induction of sperm morphological abnormalities and histopathological changes in different body organs. The drug was administrated orally at a dose of 81 mg/kg body weight twice daily (Total = 162 mg/kg/day) for various periods of time equivalent to 625 mg/men (twice daily). Results The results revealed non-significant chromosomal aberrations induced after treatment with amoxicillin/clavulanic acid (AC) in both bone marrow and mouse spermatocytes after 7 and 10 days treatment. On the other hand, statistically significant percentages of sperm morphological abnormalities were recorded. Such percentage reached 8.10 ± 0.55, 9.86 ± 0.63 and 12.12 ± 0.58 at the three time intervals tested (7, 14 and 35 days after the 1st treatment respectively) (treatment performed for 5 successive days) compared with 2.78 ± 0.48 for the control. The results also revealed histopathological changes in different body organs after AC treatment which increased with the prolongation of the period of therapy. Congestion of central vain, liver hemorrhage and hydropic changes in hepatocytes were noticed in the liver. Degenerative changes were found in kidney glomerulus and tubules while testis showed atrophy of seminiferous tubules, and reduction of spermatogenesis. AC also induced neurotoxicity and altered brain neurotransmitter levels. Hemorrhage in the myocardium, disruption of cardiac muscle fibers and pyknotic nuclei in cardiomyocytes were recorded as side effects of AC in heart tissue. Conclusions The results concluded that AC treatment induced sperm morphological abnormalities and histopathological changes in different body organs. Clinicians must be aware of such results while describing the drug.
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Background & objectives: Male reproductive function in the general population has been receiving attention in recent years due to reports of various reproductive and developmental defects, which might be associated with various lifestyle and environmental factors. This study was carried out to determine the role of various lifestyle and environmental factors in male reproduction and their possible association with declining semen quality, increased oxidative stress as well as sperm DNA damage. Methods: Semen samples were obtained from 240 male partners of the couples consulting for infertility problem. Semen analysis was carried out using WHO criteria and subjects were categorized on the basis of self reported history of lifestyle as well as environmental exposure. The oxidative and antioxidant markers; lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) as well as DNA damage by acridine orange test (AO) were determined. Results: The presence of abnormal semen parameters was significantly higher among the lifestyle and/or environmental exposed subjects as compared to the non-exposed population. Further, the levels of antioxidants were reduced and sperm DNA damage was more among the lifestyle and/or environmental exposed subjects, though the changes were not significant. Interpretation & conclusions: These findings indicated that various lifestyle factors such as tobacco smoking, chewing and alcohol use as well as exposure to toxic agents might be attributed to the risk of declining semen quality and increase in oxidative stress and sperm DNA damage.
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Omega-3 (ω-3), is long-chain, polyunsaturated fatty acids (PUFAs) of plant and marine origin. The present study was conducted to evaluate the protective effect of omega-3 against cytotoxicity and genotoxicity of anticancer drug; Azathioprine (Imuran): Male albino mice were administrated two levels; therapeutic (5mg|kg) and double therapeutic (10mg|kg) doses. Azathioprine was intraperitoneally injected for 3 times at 48 hour interval. Omega-3 was orally administered with 2 ml/kg for ten consecutive days either before or after Azathioprine treatments. At the end of experimentation period, samples of bone marrow were collected from five mice within each group for micronucleus assay. The liver and testis tissue samples were removed and stored at – 80 °C until use for DNA extraction, and determination of glutathione contents. Another animal group was treated at the same regimen and were used for the determination of sperm abnormalities and sacrificed after 35 days. The results indicated that oral administration of omega-3 either before or after treatment of Azathioprine was effective in reduction of the frequencies of Mn-PCEs, decreased the DNA fragmentation, total sperm abnormalities and significantly increased sperm count, percentage of PCEs, and enhanced the ratio of PCEs to NCEs. However, random amplified polymorphism of DNA (RAPD) showed distinct differences in animal groups intoxicated with Azathioprine before and after omega-3 treatment, which reflected DNA protective effect of omega-3. Depletion in glutathione content in testis was also observed in Azathioprine treated mice, which was improved by oral administration of Omega-3 either before or after treatment with Azathioprine.
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Ayurveda, the Indian holistic healthcare system encompasses traditional medicines with a principle of creating harmony and maintaining balance within the natural rhythms of the body. Rasayana is one of the branches of Ayurveda frequently used as rejuvenant therapy to overcome many discomforts and prevent diseases. It has been reported that rasayanas have immunomodulatory, antioxidant and antitumor functions. However, the genotoxic potential of many rasayanas remains to be evaluated. The present study was undertaken to assess the role of Brahma rasayana(BR) on genotoxicity in vivo in a mouse test system. The older mice (9 months) were orally fed with rasayana for 8 weeks. The treated groups showed no signs of dose-dependent toxicity at the dosage levels tested. The body weight loss/gain and feed consumption were unaffected at tested doses. Furthermore, sperm abnormalities and chromosomal aberrations were insignificant in the treatment group when compared to controls. However, there was a marginal increase in sperm count in the BR treated animals. These findings clearly indicate that there are no observed adverse genotoxic effects elicited by BR in experimental animals such as mice.
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Background: Oxidative stress due to improper control of blood glucose in chronic diabetes plays a major role in the development of secondary complications including cancer and birth defect. The aim of this study is to evaluate the protective effect of combination of pioglitazone with metformin or glimepiride against the experimental type-2 diabetes induced nuclear damage and reproductive toxicity in rats. Methods: The combinations of Pioglitazone (Pio-1 mg/kg) with metformin (Met-50 mg/kg) or glimepiride (Gmp-0.2 mg/kg) given orally daily for 4 weeks were tested against nicotinamide (NA- 230 mg/kg, ip)-streptozotocin (STZ-65 mg/kg, ip)-induced micronuclei (MN) formation and sperm abnormalities in male Wistar rats. The antioxidant status was evaluated by measuring the levels of serum lipid peroxidation (LPO), catalase (CAT) and superoxide dismutase (SOD). Results: The administration of Pio+Met significantly (P<0.01) reduced the number of micronucleated erythrocytes, increased the polychromatic: normochromatic erythrocytes (P/N ratio), reduced (P<0.001) sperm morphology defects and increased (P<0.05) the caudal sperm count compared to the untreated diabetic condition. Furthermore, the Pio+Met combination enhanced the antioxidant status in diabetic animals. However, Pio+Gmp did not attenuate the nuclear and sperm defects or oxidative stress. Conclusions: The observations suggest that Pio+Met combination reduced nuclear damage and sperm abnormalities by enhancing the antioxidant status in the diabetic animals.
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Intraperitoneal administration of 500 mg/kg and 625 mg/kg doses of the germ cell mutagen, ethyl methanesulphonate (EMS) in 5 consecutive days to the house rat, Rattus rattus caused a dose-dependent reduction in its body weight, cauda epididymides weight, concentration, motility and percentage of live spermatozoa with simultaneous increase in the percentage of their abnormal forms. Compared to 0·65% spermatozoa with abnormal heads in the cauda epididymidis of untreated control rats, 24·86% and 65·72% such spermatozoa were observed in rats on day 14 post treatment with 500 mg/kg and 625 mg/kg doses of EMS respectively. On day 28 post treatment corresponding values for abnormal spermatozoa were 16·21% and 14·32%. Similarly, spermatozoa with abnormal flagella increased from 0·78% in control rats to 9·25% and 5·75% on day 14 post treatment of 500 and 625 mg/kg doses of EMS respectively and declined to 2·91% and 2·40% on day 28 post treatment. Abnormality in the sperm head was mainly due to acrosomelessness and in the flagellum due to bending at proximal region. However, the main effect of EMS was the development of spermatozoa without or deformed acrosomes which may impair the fertility of rats. Analysis of various stages of differentiation of spermatozoa inthe testis revealed that population of preleptotene and pachytene spermatocytes and of round spermatids showed a gradual decline which became significantly less than controls on day 28 of EMS treatment. Occurrence of abnormal heads of testicular spermatids indicated that the sperm head abnormalities originated in the testis during late spermiogenesis.