Mona G. Amer

Epicatechin attenuates doxorubicin-induced brain toxicity: critical role of TNF-α, iNOS and NF-κB.

Doxorubicin (DOX) is considered one of the most important chemotherapeutic agents that is used for the treatment of solid tumors. Its long-term use can cause neurodegenerative disorders due to its prolonged activation of microglia. The present study proved that the use of epicatechin prior to DOX treatment significantly attenuated not only the increase in TNF-α, iNOS and NF-κB expressions but also the increase in TNF-α and total nitrite levels in brain tissue when compared with rats treated with DOX-only. Thus, our study revealed that epicatechin can be used for the treatment of neuroinflammation and also for preventing the development of neurodegenerative disease during antineoplastic therapy because of its protective role in attenuation of neurotoxic pro-inflammatory mediators including TNF-α, NF-κB, and iNOS.

Cilostazol attenuates gentamicin-induced nephrotoxicity in rats.

INTRODUCTION Gentamycin is a widely used antibiotic. The nephrotoxic adverse effects of the drug may limit its use. Cilostazol, a phosphodiesterase III inhibitor, was reported to protect from renal oxidative stress. This work aimed to investigate the possible protective effect of cilostazol on gentamicin-induced nephrotoxicity and the possible underlying mechanisms. MATERIALS AND METHODS 40 male albino rats were divided into 4 equal groups: (1) Control; (2) Cilostazol, 10mg/kg, p.o.; (3) Gentamicin, 80 mg/kg, i.p.; (4) Gentamicin 80 mg/kg, i.p. along with cilostazol 10mg/kg, p.o. All drugs were administered once daily for 8 days. On 9th day blood samples were collected for the estimation of creatinine, urea and uric acid in serum. Then the rats were sacrificed and kidneys were removed for light and electron microscope studies. Moreover, reduced glutathione (GSH) and malondialdehyde (MDA) levels as well as catalase (CAT) and superoxide dismutase (SOD) activities were determined in renal tissues. RESULTS Gentamicin elevated the serum levels of creatinine, urea and uric acid as well as the MDA level in the renal tissue, while it decreased CAT, SOD activities and GSH levels as well as produced degenerative changes in glomeruli and tubules associated with increased expression of apoptotic markers and decreased expression of anti-apoptotic markers. Administration of cilostazol decreased urea, creatinine, uric acid and MDA levels while increased CAT and SOD activities and GSH levels as well as ameliorated the histopathological changes in relation to gentamicin group. CONCLUSION Cilostazol protected rats from gentamicin-induced nephrotoxicity possibly, in part through its antioxidant and anti-apoptotic activity.

Vitamin D receptor gene polymorphisms and steroid receptor status among Saudi women with breast cancer.

The vitamin D receptor (VDR) is a mediator for the cellular effects of vitamin D and interacts with other cell signaling pathways that influence cancer development. We evaluated the associations of the FOK1 and Taq1 VDR polymorphisms and breast cancer risk and possible effect modification by steroid receptor status of the tumor. This case-control study includes 95 breast cancer patients and 100 age-matched controls. Genotyping for VDR FOK1 and Taq1 polymorphisms was performed using polymerase chain reaction-based restriction fragment length polymorphism. Level of 25(OH)D in serum was determined using ELISA. Immunohistochemical studies were performed for estrogen receptors (ER) and progesterone receptors (PR). The frequencies of ff genotype were significantly increased in the breast cancer group compared to the control group. Carriers of the f allele were significantly more likely to develop BC. We observed a statistically significant interaction for the Fok1 polymorphism and ER status. Our results demonstrated that FOK1 f. genotype and f allele have an important role in breast cancer risk in Saudi patients.

Caffeine intake decreases oxidative stress and inflammatory biomarkers in experimental liver diseases induced by thioacetamide: Biochemical and histological study:

Liver disease remains a significant global health problem. Increased caffeine consumption has been associated with a lower prevalence of chronic liver disease. This study aimed to investigate the modifying effects of caffeine on liver injury induced by thioacetamide (TAA) administration in male rats and the possible underlying mechanisms. Forty adult male rats were equally classified into four groups: control group, received only tap water; caffeine-treated group, received caffeine (37.5 mg/kg per day); TAA-treated group, received intraperitoneal (i.p.) TAA (200 mg/kg b.w.) twice a week; and caffeine + TAA-treated group, received combined TAA and caffeine in the same previous doses. After eight weeks of treatment, blood samples were collected for biochemical analysis and liver specimens were prepared for histological and immunohistochemical studies and for assessment of oxidative stress. TAA induced liver toxicity with elevated liver enzymes and histological alterations, fatty changes, apoptosis, and fibrosis evidenced by increased immunohistochemical reaction to matrix metalloproteinase-9 (MMP-9) and collagen type IV in hepatocytes. Also, the levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in serum were significantly elevated. Co-treatment with caffeine and TAA restored normal liver structure and function. Caffeine provided an anti-fibrogenic, anti-inflammatory, and antioxidant effect that was associated with recovery of hepatic histological and functional alterations from TAA-induced hepatotoxicity.

Role of calorie restriction in alleviation of age-related morphological and biochemical changes in sciatic nerve

BACKGROUND Aging is associated with structural, functional and biochemical alterations in the nervous system. Calorie restriction (CR) was found to retard most physiological indices of aging. OBJECTIVES This work aimed to investigate the effect of CR on age-related changes in sciatic nerves. MATERIALS AND METHODS Thirty male albino rats aged 1 month were equally divided into three groups; Group I [control adult-ad libitum AL]: fed a regular diet and sacrificed at the age of 6 months, group II (aged-AL group): fed a regular diet AL and sacrificed at the age of 18 months, and group III (aged CR) fed a 40% calorie restricted diet and sacrificed at the age of 18 months. Rats were anesthetized and sciatic nerves were processed for light, electron microscope and morphometric studies. Oxidative stress in sciatic nerves was investigated by estimation of lipid perioxidation by product malondialdehyde (MDA) tissue level and antioxidant enzyme; superoxide dismutase activity (SOD). RESULTS The aged (AL) sciatic nerves appeared disorganized, with thick perineurium and increased collagen fibers associated with decreased g-ratio. Abnormal myelin forms were seen as outfolded myelin loops, thin denuded myelin, splitting of myelin into myelin figures and interlamellar vacuoles. Schwann cells revealed vacuolated cytoplasm. There was also significant increase in MDA level and a significant decrease in SOD activity in comparison to control adult (AL). Apparent structural and histomorphological improvement were noticed after CR in aged rats. CONCLUSION Aging caused structural and biochemical alterations in sciatic nerves with alleviating effect of calorie restriction on such effects.

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

Introduction 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. Materials and methods 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 &mgr;g/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&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. Results 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. Conclusions 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.

The ability of hesperidin compared to that of insulin for preventing osteoporosis induced by type I diabetes in young male albino rats: A histological and biochemical study

BACKGROUND Patients with type I diabetes are at increased risk of osteoporosis even after insulin therapy in adult stage. This study was conducted to compare the efficacy of hesperidin (hesp) therapy versus that of insulin alone in the alleviation of osteoporosis arising from type I diabetes mellitus (T1DM) in young rats. MATERIALS AND METHODS Hesperidin was administered orally to STZ-induced diabetes. The animals were evaluated morphologically and biochemically and compared with that received daily SC injections of long-acting insulin. RESULTS Histologically, we observed the degeneration of osteoblasts and osteocytes, decreased collagen fibers, and disturbed bone turn over markers in untreated DM rats. Hesperidin+ insulin supplementation to diabetic rats caused significant improvement of most of the bone histological and morphometric parameters compared with the insulin-treated group. Furthermore, hesp treatment significantly reduced pro-inflammatory mediators TNFα and NF-κB and increased serum biochemical markers of bone turnover, including osteopontin (OPN), osteocalcin (OC) and decreased serum alkaline phosphatase (ALP). CONCLUSION These data demonstrated that hesp could be considered to be a beneficial drug for preventing diabetic osteoporosis in growing age.

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⩽0.03), and did not observe any association between the XPD Lys751Gln polymorphism and CRC risk. We found association between both XRCC1 A399G polymorphisms and histological grading of disease. CONCLUSION Our results suggested that, XRCC1 gene is an important candidate gene for susceptibility to colorectal carcinoma.

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

IntroductionInterferon alpha (IFN-&agr;) therapy is used considerably in Egypt because of a high prevalence rate of chronic hepatitis C virus infection. &agr;-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 optic nerve of rats after an injection of IFN-&agr; and to determine the role of ALA supplementation. Materials and methodsForty 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-&agr; alone (100000 IU/kg/three times/week, intraperitoneally). Group IV included rats that received both IFN-&agr; and ALA. After 8 weeks, the optic nerves were extirpated and processed for light and electron microscope examination. ResultsOptic nerves of the group that received IFN-&agr; showed nerve 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-&agr;. ConclusionIFN-&agr; exerted a deleterious effect on the histological structure of the optic nerve in rats and ALA supplementation minimized these effects.

Role of adipose tissue derived stem cells differentiated into insulin producing cells in the treatment of type I diabetes mellitus

Generation of new β cells is an important approach in the treatment of type 1 diabetes mellitus (type 1 DM). Adipose tissue-derived stem cells (ADSCs) might be one of the best sources for cell replacement therapy for diabetes. Therefore, this work aimed to test the possible role of transplanted insulin-producing cells (IPCs) differentiated from ADSCs in treatment of streptozotocin (STZ) induced type I DM in rats. Type 1 DM was induced by single intra peritoneal injection with STZ (50 mg/kg BW). Half of the diabetic rats were left without treatment and the other half were injected with differentiated IPCs directly into the pancreas. ADSCs were harvested, cultured and identified by testing their phenotypes through flow cytometry. They were further subjected to differentiation into IPCs using differentiation medium. mRNA expression of pancreatic transcription factors (pdx1), insulin and glucose transporter-2 genes by real time PCR was done to detect the cellular differentiation and confirmed by stimulated insulin secretion. The pancreatic tissues from all groups were examined 2 months after IPC transplantation and were subjected to histological, Immunohistochemical and morphometric study. The differentiated IPCs showed significant expression of pancreatic β cell markers and insulin secretion in glucose dependent manner. Treatment with IPCs induced apparent regeneration, diffused proliferated islet cells and significant increase in C-peptide immune reaction. We concluded that transplantation of differentiated IPCs improved function and morphology of Islet cells in diabetic rats. Consequently, this therapy option may be a promising therapeutic approach to patient with type 1 DM if proven to be effective and safe.