Histological and immunohistochemical studies on the cerebellar cortex of adult male albino rats treated with griseofulvin

Griseofulvin was the first oral anti-fungal drug available for treatment of dermatophytosis. Neurological side effects including neuropathies, confusion, vertigo, eyesight disorders and fatigue may occur due to its use. Twenty adult male albino rats, each weighing 100-150 gm were used to study the toxic effects of griseofulvin administration on the histological structure of cerebellar cortex. They were classified equally into four groups. The first group: was used as a negative control group, the second group: was used as a positive control group, each rat was given 1 mL olive oil orally daily for 12 weeks, the third group: each rat was given griseofulvin orally [dissolved in olive oil in a dose of 2500 mg/kg body weight [1/20 of LD 50]for 6 weeks and the fourth group: each rat was given griseofulvin orally [dissolved in olive oil in a dose of 2500 mg/kg body weight [1/20 of LD 50] for 12 weeks. At the time of sacrifice all the animals were anaesthetized with ether inhalation and their cerebelli were carefully dissected and processed for paraffin sections then stained with hematoxylin and eosin, Weelecks procedure and modified aldehyde thionine technique to study the general structures. Immunohistochemical stain with astroglial marker antibody Glial Fibrillary Acid Protein was also used. In griseofulvin-treated animals of the third group, there was distortion of some Purkinje cells with loss of their dendritic arbirization and they were separated from each other. In treated animals of the fourth group, some Purkinje cells were more distorted and separated by wide spaces. The molecular layer appeared with scattered cells and less abundant nerve fibers in between. Immunohistochemically, tile treated animals of the third group showed Glial Fibrillary Acid Protein positive astrocytes in the molecular and granular layers. In the fourth group, there were Glial Fibrillary Acid Protein more positive astrocytes. The results of the current study revealed that, administration of griseofulvin for a long time induced adverse effects on the histological structure of the cerebellar cortex of adult male albino rats

Comparative study between the toxic effects of rofecoxib and harpagophytum procumbens extract on adult albino rats

The highly selective cyclo- oxygenase II [COX-II] inhibitors could alleviate pain and inflammation and have fewer side effects than conventional non-steroidal anti-inflammatory drugs [NSAIDs]. Herpagophytum Procumbens has been shown to reduce inflammation and pain associated with various types of arthritis. The aim of this work was to perform a comparison between the toxic effects of Rofecoxib and Harpagophytum Procumbens [herpago] on adult male albino rats. This study included 170 adult male albino rats divided into 5 groups. Group I, II and III were used as control groups [-ve control group, Gum acacia group and distilled water group]: each consisted of 30 rats remained for 6 weeks. Group IV [rofecoxib group]: consisted of 40 rats, each rat was gavaged with 1.8 mg rofecoxib/rat [double human therapeutic dose] once daily for 6 weeks. Group V [herpago group]: consisted of 40 rats, each rat was gavaged with 86.4 mg herpago/rat [double human therapeutic dose] once daily for 6 weeks. At the end of six weeks: ten rats from rofecoxib [IV] and herpago [V] groups and fifteen rats from each control group [I, II and III] were used for blood pressure measuring. Another ten rats from groups IV and V and fifteen rats from I, II and Ill were used for biochemical and histopathological studies. The remaining rats of both groups IV and V were left for another 6 weeks without drug administration for follow up. At the end of this period the follow up rats were examined as above. Groups I, II and III showed no abnormal findings without statistically significant difference between them [P>0.05]. In rofecoxib group an increase in systolic and diastolic blood pressures [SBP, DBP] were detected with a significant difference when compared with -ve control group [P<0.001], while herpago group showed a decrease in SBP and DBP with a statistically significant difference when compared with the -ve control group [P<0.001]. After 6 weeks of follow up, the SBP and DBP of rofecoxib and herpago groups showed no significant difference when compared with the -ve control group [P>0.05]. After 6 weeks of treatment there were an increase in serum Na+ and K+ levels with a decrease in serum pH and HCO3- with a statistically significant difference in rofecoxib group when compared with the -ve control group [P<0.001]. Herpago group showed no abnormal findings in the above mentioned biochemical, parameters. Six weeks after the discontinuation of rofecoxib administration the Na+ level returned to its control level and gave no significant difference when compared with the -ye control group [P>0.05]. Serum K+, HCO3- and pH levels improved but didn't reach to the control level and gave significant difference when compared with the -ve control group [P<0.05]. Macroscopically, no abnormal findings in the heart gastro- intestinal tract [GIT] were detected in all tested groups. With rofecoxib group, microscopical examination of the cardiac sections showed ischemic changes with atrophy of cardiac muscles. Herpago group showed no histopathological abnormalities on microscopical examination. After 6 weeks of follow up histopathological examination of the heart in rofecoxib group showed disappearance of the ischaemic changes. The cardiac muscles regain its normal thickness and length. Histopathological examination of the stomach and small intestine of rofecoxib group showed different degrees of affection varies from edema of lamina propria and vascular congestion to loss of superficial epithelium [erosion] and peptic ulcer. Herpago group showed no histopathological abnormalities in the GIl. After 6 weeks of follow up in rofecoxib group partial healing of erosions and ulcers occur and the mucosa regained its normal thickness. It could be concluded that rofecoxib is more toxic than herpago and its toxic effects were partially reversible after its discontinuation

Comparative study of the hepatotoxic, genotoxic and carcinogenic effects of praziquantel distocide and the natural Myrrh extract Mirazid [R] on adult male albino rats

Praziquantel [PZQ] is widely and effectively used in the control of bilharziasis which constitutes a major endemic health problem in Egypt. However, recent studies recommended that the drug must be re-evaluated because of its potential carcinogenicity and genotoxicity. Mirazid is a new natural anti-schistosomal drug formed of myrrh extract and considered to be a safe drug. This work was conducted to evaluate and compare hepatotoxic, genotoxic and carcinogenic effects of PZQ und mirazid on adult male albino rats by assessment of serum levels of ALT, AST and bilirubin, histopathological study of the liver and cytogenetic study of bone marrow cells. 100 adult male albino rats were equally divided into 4 groups: group I negative control, group II control rats received distilled water, group III received weekly single oral dose of PZQ [1500 mg/kg] for 6 weeks and group IV received daily oral dose of mirazid [500mg/kg] for 6 weeks. At the end of the study, 10 rats of each group were investigated by assessment of the levels of AST, ALT, and bilirubin. After scarification, liver sections were examined by light microscopy. Another 10 rats of each group were submitted to cytogenetic examination. It was found that praziquantel induced a significant increase in the mean values of AST, ALT and bilirubin with areas of hyaline degeneration, fatty changes, dysplasia and necrosis in the liver sections. It also induced a significant increase in the incidence of chromosomal aberrations as polyploidy, fragment, deletion and ring chromosome as compared with control group. Mirazid induced an insignificant increase in the mean values of AST, ALT and bilirubin with a normal hepatic tissue and an insignificant increase in the incidence of chromosomal aberrations as compared with the control group. On comparing both drugs, praziquantel induced a significant hepatotoxic, genotoxic and carcinogenic effects. It was concluded that praziquantel is considered to be a hepatotoxic, genotoxic and carcinogenic drug. On the other hand, mirazid seemed to be a safe and promising antiparasitic drug, free from hepatotoxic, genotoxic and carcinogenic effects

protective role of - tocopherol as an antioxidant against 2 - nitropropane toxicity in albino rats

2-Nitropropane [2-NP] is an important industrial solvent and a component of cigarette smoke. It is mutagenic in bacteria and carcinogenic in rats.The liver is the target organ in 2-NP -treated rats. This study was conducted on 480 adult male and female albino rats to evaluate the genotoxic and hepatotoxic effects of 2-NP and to evaluate the protective role of alpha -tocophero L. The rats were divided into 8 groups equally. The 1[st] group: was used as a negative control group to measure the basic parameters; the 2[nd]. Group [positive control group]: Each rat was given 2 C.C. distilled water twice weekly by gavage for 12 weeks; the 3[rd] group: Each rat was given 2 C.C. corn oil daily by gavage for 13 weeks; the 4[th] group: Each rat was given; 2 C.C. corn oil containing alpha-tocopherol 100 mg/kg daily by gavage for 13 weeks; the 5[th] group: Each rat was given 2 C.C. distilled water containing 1/10 of the LD50 of 2-NP [50 mg/kg] twice weekly by gavage for 12 week.; the 6[th] group: Each rat was given alpha-tocopherol [100mg/kg] daily for 13 weeks and 2-NP [50 mg/kg] [started one week after the begining. of alpha-tocopherol] twice weekly by gavage for 12 weeks; the 7[th]. group: Each rat was given 2 C.C. distilled water containing 1/5 of the LD50 of 2-NP [l00mglkg] twice weekly by gavage for 12 weeks and the 8[th],. group: Each rat was given alpha-tocopherol [100mg/kg] daily for 13 weeks and 2-NP [I00 mg/kg] [started one week after the begining of alpha-tocopherol] twice weekly by gavage for 12 weeks. Every 4 weeks, 10 rats from each group were used for studying their chromosomal pattern and another 10 rats were used for histopathological and electron microscopical examination of the liver .Regarding cytogenetic study, 2-NP groups showed a significant increase in chromosomal aberrations when compared with the control group throughout the period of the study.The effect of 2-NP showed a progression that was time dependent but was not dose dependent. The frequencies of chromosomal aberrations induced in 2-NP + alpha-tocopherol groups were less than that induced in 2-NP groups indicating that, alpha-tocopherol has a partial protective effect against 2-NP genotoxicity. Regarding histopathological and electron microscopy study, 2-NP [50 mg/kg] group and [2-NP [50mg/kg] + alpha.-tocopherol] group showed mild toxic hepatitis allover the period of the study, meaning that alpha- tocopherol was not effective against toxic hepatitis induced by 2-NP [50mg/kg]. While in 2-NP [100mglkg] group, hepatic lesions started as mild dysplesia then hepatocellular carcinoma developed by the end of the study. In [2-NP [l00mg/kg] + alpha- tocopherol] group,hepatic histopathological and electron microscopical results of this group were improved when compared with 2-NP[l00mg/kg] group, meaning that alpha-tocopherol was partially effective in protection against hepatic carcinogenicity induced by 2-NP[100mg/kg]. It can be concluded that, 2-NP is genotoxic and hepatotoxic in albino rats and alpha-tocopherol has a partial protective effect against these toxicities

Immunotoxicity and thyrotoxicity of polychlorinated biphenyls [PCBS] in human and experimental animals

Since polychlorinated biphenyls [PCBs] are among the most persistant and abundant chlorinated hydrocarbon contaminants that create a potential health hazard for human beings and animals, it was the aim of the present study to shed light on the effects of PCBs on some important immune factors in workers and experimental animals and evaluate the effects of PCBs on the level of thyroid hormones that may alter the neurodevelopmental process in human. The level of immunoglobulins [IgG and IgM] were detected in the sera of workers exposed to PCBs in their blood and also the level of IgG and IgM were detected in the sera of albino rats after exposure to PCBs with detection of IgE that bind to specific cell surface receptors on tissue mast cells. Serum IgG and IgM level were estimated by an Enzyme Linked immuno Sorbant Assay [ELISA]. Rats were sacrificed to study mast cell degranulation .The level of thyroid hormones: Triiodothyronine [T3], Thyroxine [T4] and Thyroid Stimulating Hormone [TSH] were detected on workeres and experimental animals as an indicator for thyrotoxicity of PCBs. The results had shown a significant decrease in IgG and IgM with increased degranulation of mast cells as an indicator of immunotoxicity and decrease in thyroid hormones levels as an indicator of thyrotoxicity

Light and electron microscope study of the lead effect on the testis of adult albino rats

Ten adults [three months old] male albino rats weighing 250-300gm were used in this study aiming to get insight on the histological alterations in the testes of chronically lead exposed adult rats in an attempt to clarify the mechanism of action of lead on the male reproductive system. The animals were divided into two equal groups, a control group and an experimental one. Animals of the first group were injected intraperitoneally by an equivalent doses of normal saline. Animals of the second group were injected intraperitoneally by lead acetate at a dose of 8mg/kg body weight/day, 5days/week for five successive weeks. At the time of sacrifice, the animals were anaesthetized with ether inhalation and their testes were carefully dissected and processed for light and electron microscope examination. Light microscope examination of the testes of lead treated rats revealed the presence of irregularities in the outlines of the affected seminiferous tubules, disorganization and sloughing of their germinal epithelium into their luminae. Also, there was arrest of spermatogenesis in most of the affected tubules. Electron microscope examination of the testes of the lead treated rats showed that some of spermatogonia appeared with large vacuoles and distorted nuclei. The nuclei of primary spermatocytes showed loss of their membranes and fragmentation of their chromatin. The spermatids had few mitochondria, large lysosomes and degenerated nuclei. While Sertoli cell cytoplasm contained large vacuoles and distorted mitochondria. Also, there was disruption of tight junction between their lateral processes. The midpieces of the sperms revealed markedly affected axonemes and both fibrous and mitochondrial sheathes. The cytoplasm of Leydig cells contained many vacuoles, few lipid droplets and their nuclei had much peripheral heterochromatin. From this study, it could be concluded that lead has a harmful effect on the male reproductive system through a direct influence on the histological structure of the testis