DNA repair genes polymorphisms and risk of colorectal cancer in Saudi patients

Background and study aims: Polymorphisms in the DNA repair genes may influence individual capacity to repair DNA damage, which may be associated with increased genetic instability and carcinogenesis. Our aim was to evaluate the relation of genetic polymorphisms in 2 DNA repair genes, XPD Lys751Gln and XRCC1 [A399G], with colorectal cancer [CRC] susceptibility. We further investigated the potential effect of these DNA repair variants on clinicopathological parameters of CRC patients

Patients and methods: Both XPD and XRCC1 polymorphisms were characterised in one hundred CRC patients and one hundred healthy controls who had no history of any malignancy by polymerase chain reaction restriction fragment length polymorphism [PCR-RFLP] method and PCR with confronting two-pair primers [PCR-CTPP], using DNA from peripheral blood in a case control study

Results: Our results revealed that the frequencies of GG genotype of XRCC1 399 polymorphism were significantly higher in the CRC patients than in the normal individuals [p

Conclusion: Our results suggested that, XRCC1 gene is an important candidate gene for susceptibility to colorectal carcinoma

Protective role of curcumin against 2,3,7,8-tetrachlorodibenzo-dioxin-induced histological and biochemical changes in fundic mucosa of the adult rat stomach

2,3,7,8-Tetrachlorodibenzo-dioxin [TCDD] is released into the environment from different activities and industrial sources, with a higher incidence of gastric exposure. This work aimed to study the histological and biochemical changes induced by TCDD in the fundic mucosa and the possible protective role of curcumin against these changes. Thirty adult female albino rats were classified into three groups: the control group [group I]; the TCDD group [group II], in which rats received 100 microg/kg TCDD orally for 3 months; and the curcumin+TCDD group [group III], in which rats received an oral dose of 80 mg/kg curcumin in concurrence with TCDD for 3 months. The serum level of the gastrin hormone was measured. Samples from the fundus of the stomach were stained with H and E, Van Gieson, and PAS/alcian blue and for immunohistochemical detection of aryl hydrocarbon receptors [AHR] and chromogranin A. Morphometric and electron microscopic studies were also carried out. Hyperplasia and metaplastic mucosal changes, together with enteroendocrine cell hyperplasia, were evident. Moreover, glandular degeneration, areas of atrophic gastritis, cellular apoptosis, and gastric ulcers were detected. The previous results could be explained by both TCDD-induced hypergastrinemia and increased AHR expression. In contrast, curcumin appeared to have a propitious protective effect against TCDD-induced gastric affection. Most of the TCDD-induced gastric changes were not observed in group III. It was concluded that the gastric mucosa is sensitive to the toxic effects of TCDD and curcumin can be used to avoid TCDD-induced gastric complications

structure of the optic nerve after the administration of interferon alpha-2a in adult male albino rats and the role of alpha-lipoic acid supplementation

Interferon alpha [IFN-alpha] therapy is used considerably in Egypt because of a high prevalence rate of chronic hepatitis C virus infection. Alpha-Lipoic acid [ALA] has been found to play a neuroprotective role in many insults. The aim of this study is to observe the histological structure of the topic nerve of rats after an injection of IFN-alpha and to determine the role of ALA supplementation. Forty adult male albino rats were divided equally into four groups. Group I served as the control group. Group II included rats that received ALA alone [100mg/kg/day, intraperitoneally]. Group III included rats that received IFN-alpha alone [100000 IU/kg/three times/week, intraperitoneally]. Group IV included rats that received both IFN-alpha and ALA. After 8 weeks, the optic nerves were extirpated and processed for light and electron microscope examination. Optic nerves of the group that received IFN-alpha showed nerved damage manifested as axonal damage and changes in the myelin sheath. Neuroglia showed vacuolation in their cytoplasm and heterochromatic nuclei. Morphometric and statistical analyses showed a significant increase in the surface area of positive glial fibrillary acidic protein astrocytes, indicating reactive astrogliosis. Blood capillaries were distorted with ill-defined walls and protrusion of the endothelial cells into their lumina. These changes were limited by concomitant ALA supplementation with IFN-alpha. IFN-alpha exerted a deleterious effect on the histological structure of the optic nerve in rats and ALA supplementation minimized these effects

Influence of Gibberellic Acid [GA3] on Renal Cortex of Adult Male albino Rats [Histological, Immunohistochemical and Biochemical Study]

Plant growth regulators [PGRs] especially gibberellic acids [GA3] are widely used in Egypt to increase plant size, production and to increase plant availability all the year. Little is known about the biochemical or physiological effects of GA3 in mammalian tissues. This study aimed to evaluate the histological, immunohistochemical and biochemical changes in the rat renal cortex with subacute and subchronic exposure to GA3 and to detect the possible mechanism of such toxicities. Fifty adult male albino rats were classified into control group [I], experimental group [IIa and IIb] received GA3 in a dose of 75ppm [part per million]. Seventy five parts per million of GA3 as drinking water for 2weeks in subgroup IIa [subacute exposure] and for 8 weeks in subgroup IIb [subchronic exposure]. Group III [recovery group]: Rats received GA3 for 8weeks and stopped for other 6weeks. Renal cortex was stained with H and E, Masson's trichrome, immunohistochemically for Bcl-2 protein and electron microscopic examination. Oxidative biomarker [MDA] was detected in kidney tissue and antioxidant enzymes were detected in erythrocyte pellets prepared from blood sample. GA3 administration in group [II], led to degeneration, necrosis, apoptosis of the epithelial cells lining some of the tubules of the renal cortex with subacute toxicity and in most of the tubules with subchronic toxicity, fibrosis is significantly apparent in the subchronic subgroup. Interstitial cellular infiltration and hemorhage were seen. Hyaline casts in the lumen of renal tubules were apparent in the subchronic subgroup. Area percentage of antiapoptotic protein Bcl-2 immunoreactivity was decreased in the subchronic subgroup. Picture of cystic glomerular atrophy, acute tubular necrosis, degenerated podocytes and thickened blood renal barrier became prominent in the subchronic subgroup. The histological changes were associated with biochemical markers of oxidative stress. These changes were reduced in the recovery group but not retained to normal and the picture of oxidative stress was still present. The findings implied that gibberellic acid [GA3] induced nephrotoxic effect associated with oxidative stress with some sort of self recovery after stoppage of exposure. So, gibberellic acid should be used cautionary. Also, producers and consumers should be in conscious on the probable toxic effects of these chemicals

Possible protective role of L-carnitine on diclofenac induced hepatotoxicity in adult male albino rats [histological, immunohistochemical and biochemical study]

Diclofenac [DCLF] is in common use worldwide as non steroidal anti-inflamatory drugs [NSAIDs] that have been reported to cause significant adverse effects. L-Carnitine has been proposed as antioxidant because it helps reduce oxidative stress. This work aimed to study the possible histological, immunohistochemical and biochemical changes of liver associated with diclofenac administration and to assess possible beneficial role L- carnitine [LC] on diclofenac [DCLF] induced hepatotoxicity. Fifty adult male albino rats were divided into 4 main groups. Group I: Served as positive and negative controls. Group II: Received LC in a dose of 50 mg/ kg intramuscular [IM] in 1 ml saline. DCLF treated group [III]: Received DCLF 50 mg/ kg IM in 1 ml saline. Combined group [IV]: Rats received LC then DCLF after 2 hours IM. The treatments were given for the rats 6 days/ week for two weeks. At the time of sacrifice, the rats were anaesthetized; blood samples were taken for measuring liver function tests. Specimens from the liver of each rat were taken for light and electron microscopic examination. Histological examination of the liver of the rats of DCLF treated group revealed different degrees of focal lobular affection. Enlarged portal areas, congested portal and central veins, bile duct proliferation, cellular infiltration and fibrosis were detected. Significant decrease in area% of brown positive immunoreactions for glutathione peroxidase I [GPXI] was detected in comparison with control group. Necrosis of most of hepatocytes especially in those close to portal area was detected. Most of hepatocytes mitochondria appeared with ruptured membrane. Pretreatment with LC in combined group showed slight histological changes with sinusoidal congestion, minimal fibrosis around prominent portal area with significant increase in area% of GPX1 in comparison with DCLF treated group. Most of mitochondria appeared with intact membrane. There were significant elevations in liver function tests in DCLF treated group when compared with other groups with partial recovery in combined group. Results obtained in this study demonstrated that high doses of DCLF induced histological and biochemical changes in the liver due to oxidative stress and that the use of LC had partially reduced the DCLF induced toxicity. This may suggest that LC enhanced antioxidant defence and may be used as a cell protector for DCLF induced hepatotoxicity

Histological changes induced by experimental renal failure in the lung of adult male albino rats and the role of melatonin supplementation

Chronic renal failure may affect virtually every system in the body. The most common uremic consequences in the respiratory tract are disturbed pulmonary function and weak respiration. The present study was designed to evaluate the histological changes induced by experimental renal failure in the lung of adult male albino rats and the possible protective role of melatonin as antioxidant. Forty five adult male rats were equally classified into control group and two experimental groups [15 animals each]. In experimental group I, the rats were submitted to experimental renal failure by five sixths renal ablation. In group II, the nephrectomized rats were treated with melatonin [10 mg/l00 ml/day] orally for 12 weeks. The development of renal failure was monitored by serial estimation of serum creatinine and urea levels. At the time of sacrifice, all rats were anesthetized with ether and their lungs were dissected out and processed for light and electron microscope examination. The nephrectomized rats showed significant elevation in serum creatinine and urea levels. Light microscope examination of their lungs revealed massive cellular infilteration and congestion of blood vessels with marked thickening of their walls. The bronchiolar epithelium was distorted. Some collapsed alveoli appeared with narrow spaces. They were separated by thick interalveolar septa containing cellular infilteration, red blood cells, congested capillaries and fibrous tissue. Intra-alveolar macrophages and red blood cells were seen. Furthermore, electron microscope examination revealed pneumocyte type II with indented nuclei, few microvilli and loss of their secretory granules. Some collapsed alveoli were seen with thick interalveolar septa containing abundant collagen fibers and congested blood capillaries. Disorganized blood air barriers were observed. The nephrectomized rats treated with melatonin showed non significant elevation in serum creatinine and urea levels. Light microscope examination of their lungs revealed intact bronchioles and alveoli with some congested blood vessels and few cellular infilteration. Electron microscope examination showed intact pneunocyte type II and blood air barrier. The present study revealed that experimental renal failure induced adverse effects on the histological structure of the lung which was partially improved by melatonin supplementation. Clinical and experimental studies are recommended to explore the efficacy of melatonin in renal failure. If proven effective, melatonin would be an adjunctive therapy, since it is natural, orally administrated and relatively safe