Hesham N. Mustafa

Prophylactic role of coenzyme Q10 and Cynara scolymus L on doxorubicin-induced toxicity in rats: Biochemical and immunohistochemical study

Objective: The study aims to evaluate the protective effects of coenzyme Q10 (CoQ10) and Cynara scolymus L (CS) on doxorubicin (dox)-induced toxicity. Materials and Methods: Sixty male rats were divided into six groups. Group 1 as a control. Group 2 received dox (10 mg/kg) intraperitoneally. Group 3 received CoQ10 (200 mg/kg). Group 4 received CS (500 mg/kg). Group 5 received CoQ10 (200 mg/kg) and dox (10 mg/kg). Group 6 received CS (500 mg/kg) and dox (10 mg/kg). The rats were then evaluated biochemically and immunohistochemically. Results: Dox produced a significant deterioration of hepatic and renal functional parameters. Moreover, an upsurge of oxidative stress and nitrosative stress markers. The expression of alpha-smooth muscle actin (α-SMA) was increased and proliferating cell nuclear antigen (PCNA) expression was decreased. Administration of CoQ10 and CS resulted in a significant improvement of hepatic and renal functional parameters, and an improvement of both α-SMA and PCNA. Conclusion: It is concluded that pretreatment with CoQ10 and CS is associated with up-regulation of favorable protective enzymes and down-regulation of oxidative stress. That can be advised as a supplement to dox-treated patients.

Protective role of CoQ10 or L-carnitine on the integrity of the myocardium in doxorubicin induced toxicity

Doxorubicin (DOX) is a chemotherapeutic agent used for treatment of different cancers and its clinical usage is hindered by the oxidative injury-related cardiotoxicity. This work aims to declare if the harmful effects of DOX on heart can be alleviated with the use of Coenzyme Q10 (CoQ10) or L-carnitine. The study was performed on seventy two female Wistar albino rats divided into six groups, 12 animals each: Control group; DOX group (10mg/kg); CoQ10 group (200mg/kg); L-carnitine group (100mg/kg); DOX+CoQ10 group; DOX+L-carnitine group. CoQ10 and L-carnitine treatment orally started 5days before a single dose of 10mg/kg DOX that injected intraperitoneally (IP) then the treatment continued for 10days. At the end of the study, serum biochemical parameters of cardiac damage, oxidative stress indices, and histopathological changes were investigated. CoQ10 or L-carnitine showed a noticeable effects in improving cardiac functions evidenced reducing serum enzymes as serum interleukin-1 beta (IL-1 β), tumor necrosis factor alpha (TNF-α), leptin, lactate dehydrogenase (LDH), Cardiotrophin-1, Troponin-I and Troponin-T. Also, alleviate oxidative stress, decrease of cardiac Malondialdehyde (MDA), Nitric oxide (NO) and restoring cardiac reduced glutathione levels to normal levels. Both corrected the cardiac alterations histologically and ultrastructurally. With a visible improvements in α-SMA, vimentin and eNOS immunohistochemical markers. CoQ10 or L-carnitine supplementation improves the functional and structural integrity of the myocardium.

Does allicin combined with vitamin B-complex have superior potentials than α-tocopherol alone in ameliorating lead acetate- induced Purkinje cell alterations in rats? An immunohistochemical and ultrastructural study

BACKGROUND The current article aims to explore the protective potentials of α-tocopherol alone and the combination of allicin and vitamin B-complex against lead-acetate neurotoxicity on the cerebellar cortex. MATERIALS AND METHODS Forty rats were divided into four groups (n = 10). Group 1 was the control group; Group 2 received 10 mg/kg body weight (BW) of lead acetate; Group 3 was exposed to 10 mg/kg BW of lead acetate plus a combination of allicin (100 mg/kg BW) and vitamin B-complex (40 mg/kg BW); Group 4 was administered lead acetate (10 mg/kg BW) and α-tocopherol (100 mg/kg BW). The animals received the treatment for 60 days by oral gavage. All the groups were studied ultrastructurally and immunohistochemically with glial fibrillary acidic protein (GFAP). RESULTS The affected groups revealed shrunken and degenerated Purkinje cells with irregular nuclei. The cytoplasm comprised several lysosomes, unhealthy mitochondria, and dilated Golgi saccules. The myelinated nerve fibres demonstrated breaking of the myelin sheaths, apparent vacuoles, and broad axonal spaces. Immunohistochemically, there was a tremendous surge in GFAP-positive astrocytes in the lead acetate-treated group. These histological and ultrastructural variations were ameliorated by the administration of a-tocopherol and the combination of allicin and vitamin B complex. Moreover, an apparent decrease in the number of GFAP-positive astrocytes was obvious in the protected groups. CONCLUSIONS Although both a-tocopherol and the combination of allicin and vitamin B-complex can be used as possible adjuvant therapies to ameliorate nervous system ailments attributable to lead acetate, α-tocopherol showed more protective potential.

Effect of Sodium Selenite and Vitamin E on the Renal Cortex in Rats: An Ultrastructure Study

This study examined the use of vitamin E to alleviate toxic effects of sodium selenite. Adult male albino rats (n=50) was divided into five groups. Group 1 was control, Groups 2 and 4 were treated with sodium selenite (2 mg/kg) for 2 and 4 weeks, respectively, Groups 3 and 5 were treated with sodium selenite (2 mg/kg) and vitamin E (100 mg/kg) for 2 and 4 weeks, respectively. Renal tissues were studied using anti-BCL2 and examined ultrastructurally. Positive Bax immunoreactivity was detected after 2 and more positive after 4 weeks and nearly all groups improved with co-administration of vitamin E. Ultrastructural study revealed lesions in Bowmans capsule and proximal convoluted tubules. The submicroscopic study revealed damage and necrosis of cortical structures after 2 and 4 weeks, respectively. After 4 weeks, cellular changes were seen, such as vacuolation and moderate degeneration of cells, widening of the urinary space scattered through the cortex with loss of cellular details, formation of apical buds, degeneration, and cellular rupture. Present findings disclosed an ameliorative effect of adding vitamin E to sodium selenite-induced changes in cortical tissues. Clinically, it is advised to add vitamin E to avoid selenium overdose hazards.

The role of curcumin in streptozotocin-induced hepatic damage and the trans-differentiation of hepatic stellate cells.

Diabetic patients frequently suffer from non-alcoholic steatohepatitis. The current study aimed to investigate the role of curcumin and the response of hepatic stellate cells in streptozotocin (STZ)-induced hepatic damage. Sixty male rats were divided into three groups. The normal control injected with a citrate buffer vehicle and the diabetic control group which was injected intraperitoneally (IP) with a single-dose of streptozotocin (50mg/kg body weight) and a diabetic group was treated with an oral dose of curcumin at 80 mg/kg body weight daily for 60 days. Curcumin effectively counteracts oxidative stress-mediated hepatic damage and improves biochemical parameters. Alpha-smooth muscle actin (α-SMA) was significantly reduced, and insulin antibodies showed strong positive immunoreactivity with curcumin administration. These results optimistically demonstrate the potential use of curcumin, which is attributed to its antiradical/antioxidant activities and its potential β-cell regenerative properties. Also, it has the capability to encourage the trans-differentiation of hepatic stellate cells into insulin-producing cells for a period of time. In addition, as it is an anti-fibrotic mediator that inhibits hepatic stellate cell activation and the transition to myofibroblast-like cells, this suggests the possibility of considering curcumins novel therapeutic effects in reducing hepatic dysfunction in diabetic patients.

The ameliorative potential of Hyphaene thebaica on streptozotocin-induced diabetic nephropathy

BACKGROUND Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. The aim of the current study is to investigate the possible beneficial effects of Hyphaene thebaica in DN. MATERIALS AND METHODS For this, 50 male albino rats were divided into five groups: group I - represented the control group; group II - received Hyp-haene thebaica extracts of 150 mg/kg BW by oral gavage for 6 weeks; group III - received single intraperitoneal injections of streptozotocin (50 mg/kg BW) to induce type-2 diabetes mellitus; group IV (protective) - diabetic rats recei-ved Hyphaene thebaica extract (150 mg/kg BW) orally for 6 weeks; group V (curative) - received Hyphaene thebaica extract (150 mg/kg BW) orally after the diagnosis of DN. RESULTS In the DN protected group, blood glucose, urea, and creatinine decreased significantly, while insulin and C-peptide increased significantly. Moreover, cystatin C and neutrophil gelatinase-associated lipocalin decreased. Collagen fibre deposition is increased with an apparent thickening of the parietal layer of Bowmans capsules and the basal lamina of convoluted tubules, as well as increase of the immune-reaction of caspase-3 and desmin. The introduction of Hyphaene thebaica led to greater amelioration in the biochemical markers, apoptotic alterations, and podocyte injuries of the protected group than in the curative group. CONCLUSIONS Hyphaene thebaica may be advised as a good choice that can delay diabetic renal complications.

Effect of Acrylamide on Stomach, Cerebellum and Testis of the Albino Rat (PPT) 3.12.2008

Acrylamide has several effects toxic and carcinogenic. The current project aimed at exploring the harmful effects of acrylamide on the structure of the stomach, cerebellum and testis in the albino rat, in an attempt to clarify its potential risk on the human health. The stomach, testis and cerebellum specimens were collected form fifty adult male albino rats. The animals were divided into two main groups. Group (I) was subdivided into 3 subgroups, control, Ia that received acrylamide in a dose of 25mg/kg/10days (P.O.) and Ib that received acrylamide in a dose of 25mg/kg/10days (I.P.). Group (II) was subdivided into 3 subgroups, control, IIa that received acrylamide in a dose of 50mg/kg/10days (P.O.) and IIb that received acrylamide in a dose of 50mg/kg/10days (I.P.). At the end of the experiment, all rats were anesthetized using ether inhalation. Specimens from testis, cerebellum and stomach were extracted and processed for light and electron microscopic examination. For the light microscope serial sections 5-6µm thick obtained, stained with HE Feulgen stain (Testis) and silver stain (Modified Glees) (Cerebellum). Testicular specimens were studied with the Image analysis technique so as to assess cellular apoptosis. Moreover, DNA cytometry of the basal compartment of the testis was performed. In the present work, it was found that the testis of the group treated with a dose of 25mg/kg/10days showed mild affection whether acrylamide was administered orally or intraperitoneally. On the other hand, the testis of the group treated with a dose of 50mg/kg/10days showed damage especially with the intraperitoneal administration in comparison to the oral treatment. This was in the form of degeneration of germ cells, numerous multinucleated giant cells with sloughed seminiferous epithelium, and vacuolations in-between the germ cells. In addition, feulgen stain was performed to assess the effect of acrylamide on cellular apoptosis in the testis. It was clearly proved that acrylamide at a dose of 50mg/kg/10days showed increased apoptosis. Image analysis of the feulgen stained sections was performed to evaluate the carcinogenicity of acrylamide on testis. It was found that acrylamide at a dose of 50mg/kg/10days showed increased abnormal DNA content in cells, which was considered a reliable marker for malignancy. As regards effect of acrylamide on the cerebellum, it was concluded that the Purkinje cells were target cells to the acrylamide. Rats treated at a dose of 25mg/kg/10days showed that Purkinje cells somata appeared unaffected, while degeneration of Purkinje cells dendrites and corresponding axons were evident in the molecular and white matter respectively. Furthermore, rats treated with 50mg/kg/10days showed argyrophilic Purkinje cells somata and their dendrites were clearly evident in the Purkinje cell and molecular layers respectively. Also, Purkinje cell axon degeneration was observed in the white matter in the form of fragmented, linearly arrayed debris. The intraperitoneal treatment showed more damage as compared to the oral one. The stomach of animals treated with acrylamide in a dose of 25mg/kg/10days showed no gastric affection, while there were mild degenerative changes and an apparent increase in mucous secreting cells in the group that received 50mg/kg/10days. The present study pointed out the hazards of acrylamide and its possible effect on human health. Recommendations are necessary to decrease acrylamide level in different foods and ways to decrease acrylamide formation during preparation of the different foods should be advertised.

Protective effect of garlic extract against maternal and foetal cerebellar damage induced by lead administration during pregnancy in rats

BACKGROUND In spite of its industrial usefulness and varied daily uses, lead (Pb) pollution is a widespread ecological problem that faces the humans in the 21th century. Pb was found to produces a wide range of toxic effects including neurotoxicity especially to the developing and young offspring. Recently, the utilisation of herbal plants has received a significant attention where there has been rising awareness in their therapeutic use; among these is the garlic. In light of the above, the current study is designed experimentally in female pregnant rats in order to investigate the beneficial role of garlic extract in the protection from the maternal and foetal cerebellar damage produced by administration of different doses of Pb during pregnancy. MATERIALS AND METHODS Positively pregnant female rats were divided into five groups; one control group, two Pb-treated groups (exposed to 160 and 320 mg/kg b.w. of Pb, respectively) and two groups treated with both Pb and garlic (exposed to Pb as previous groups together with 250 mg/kg b.w./day of garlic extract). Treatments started from day 1 to day 20 of pregnancy, where the mother rats of different experimental groups were sacrificed to obtain the foetuses. Pb level in the maternal and foetal blood and cerebellum was estimated by spectrophotometry. Specimens of the cerebellum of different mother and foetal groups were processed to histological and immunohistochemical staining for microscopic examination. RESULTS The results showed that administration of Pb to pregnant rats resulted in a dose-dependent toxicity for both mothers and foetuses in the form of decrease in maternal weight gain, placental and foetal weights, brain weight and diminished foetal growth parameters, which were prominent in rats group treated with larger dose of Pb. In Pb-treated rats, Pb level in blood and cerebellum was high when compared with the control group. The histopathological examination of the cerebellum of treated dams and foetuses showed marked alterations mainly in the form of Purkinje cell degeneration and lack of development of foetal cerebellum. Co-treatment of garlic extract along with Pb resulted in a significant decrease in Pb levels as compared with those treated with Pb alone with improvement of the histopathological changes. CONCLUSIONS This study was useful in evaluating the hazardous effects of uncontrolled use of Pb in general and in assessing the developmental and neurotoxicity of foetuses due to exposure during pregnancy in particular. Co-administration of garlic has beneficial effects in amelioration of Pb-induced neurotoxicity and reversing the histopathological changes of the cerebellum of mother rats and foetuses. (Folia Morphol 2018; 77, 1: 1-15).

Ameliorative potentials of a combination of fenugreek and alpha-tocopherol on cadmium induced testicular toxicity: An ultrastructural study

Methods. Thirty adult male albino rats divided into three equal groups 10 rats each. Group I is the control group. Group II received 5 mg/kg/day cadmium chloride. Group III received 5 mg/kg/day cadmium chloride and 150 mg/kg/day fenugreek and 100 mg/kg/day of αtocopherol. The treatment of all groups was done by oral gavage for 60 consecutive days. The testes were removed and subjected to histopathological and ultrastructure study.