Afrah F. Salama

Propolis protection from reproductive toxicity caused by aluminium chloride in male rats

Different forms of aluminium (Al) are environmental xenobiotics that induce free radical-mediated cytotoxicity and reproductive toxicity. Propolis has been reported to be important antioxidant. Therefore, this study aimed at elucidating the protective effects of propolis against reproductive toxicity of aluminium chloride (AlCl3) in male rats. The first group served as control. Group 2 received 34 mg AlCl3/kg bw (1/25 LD50). Group 3 was administered 50 mg propolis/kg bw/day. Group 4 was treated with AlCl3 plus propolis. Treatment was continued for 70 days. AlCl3 caused a decrease in testes, seminal vesicle and epididymis weights, sperm concentration, motility, testosterone level and the activities of 17-ketosteroid reductase, CAT and GST, and GSH content. While, dead and abnormal sperm and testes TBARS concentrations were increased. In the AlCl3-treated group, histopathologic examinations revealed apparent alterations in the testes, where it induced marked lesions in seminiferous tubules. Propolis alone decreased dead and abnormal sperm and TBARS, and increased testosterone, GSH, 17-ketosteroid reductase, CAT and GST. Results showed that propolis antagonized the harmful effects of AlCl3. This was proved histopathologically by the great improvement in testes. In conclusion propolis could be effective in the protection against the reproductive toxicity of AlCl3.

Methylenetetrahydrofolate Reductase Gene Polymorphisms in Egyptian Women with Unexplained Recurrent Pregnancy Loss

AIMS This work aims at testing for the association of the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with unexplained recurrent pregnancy loss (RPL) among Egyptian women. SUBJECTS AND METHODS Participants were 70 cases having a history of two or more events of unexplained RPL and 136 controls with a good obstetric history. Detection of MTHFR C677T and A1298C mutations was done by polymerase chain reaction with restriction fragment length polymorphisms assay using restriction enzymes HinfI and MboII respectively. RESULTS Compared with controls, cases with unexplained pregnancy loss showed higher frequency of the homozygous mutant MTHFR 677 TT, 1298 CC genotypes, and the mutant haplotype 677T/1298C, although not reaching statistical significance. The frequency of 677 mutant genotypes (TT or TC) combined with either the mutant 1298 (CC or AC) or normal 1298 (AA) genotypes was significantly increased among cases with late-stage pregnancy loss versus those with early-stage pregnancy loss (p=0.001). There was also increased frequency of the 677 mutant genotypes among cases with secondary infertility compared with those with primary infertility and among cases with pregnancy loss >4 times compared with those with ≤4 times but with no statistical significance. Regarding other risk factors, it was noted that the frequency of mutations among cases with no or just one risk factor did not differ significantly from those having two or more risk factors (p=0.98). CONCLUSIONS Mutations related to the MTHFR gene are increased but not statistically significant in Egyptian women with unexplained pregnancy loss. Interaction with other genetic variants might be speculated and need to be investigated.

Trehalose enhances the antitumor potential of methotrexate against mice bearing Ehrlich ascites carcinoma

Methotrexate (MTX) is commonly used as a standard chemotherapy for many cancers, however its usage required high doses thereby leading to severe adverse effects. In a trial to find a suitable neoadjuvant therapy to decrease MTX dosage without lowering its chemotherapeutic efficacy, we investigated the antitumor effect of trehalose (TRE) on mice bearing Ehrlich ascites carcinoma (EAC) and checked whether TRE can enhance the antitumor potential of MTX. Treatment with TRE induced anti-tumor effects against EAC as reveled by a remarkable decrease in body weight, tumor volume, count of viable tumor cells, expression of the anti-apoptotic gene Bcl2 as well as by a significant increase in mean survival time, life span and expression of the apoptotic gene caspase-3. TRE also caused a significant decrease in autophagic activity of EAC cells as evident by reduction in the expression of the autophagic gene Beclin 1 (Bec1) and the fluorescence intensity of autophagosome marker. Additionally, TRE restored the altered hematological and biochemical parameters and improved the disrupted hepatic tissues of EAC-bearing mice. Interestingly, co-administration of TRE and MTX showed highest anti-tumor effect against EAC. These data indicate that TRE enhances the antitumor potential of MTX and could be used as neoadjuvant drug to increase the efficacy of the antitumor drug, MTX.

Protective role of L-carnitine and vitamin E on the testis of atherosclerotic rats

Atherosclerosis is a condition caused by lipid build-up and inflammation in the arteries, so hyperlipidemia is the major reason for atherosclerosis. Testis was found to be negatively affected by hyperlipidemia which leads to its impaired functions. Vitamin E and l-carnitine have well-known lipid-lowering and antioxidative activities. Triton WR 1339 is a non-ionic detergent, which induces severe hyperlipidemia by inhibition of lipoprotein lipase. The present study evaluates the protective role of vitamin E and l-carnitine on the testis in atherosclerosis and detects the most effective choice for protection against atherosclerosis; vitamin E, l-carnitine or a combination of both. A total of 80 albino male rats were divided into eight groups (10 rats for each group): control (G1), triton (G2), l-carnitine (G3), triton + l-carnitine (G4), vitamin E (G5), triton + vitamin E (G6), l-carnitine + vitamin E (G7) and triton + l-carnitine + vitamin E (G8). Data showed a significant increase in the levels of total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), 17 beta hydroxysteroid dehydrogenase (17 β HSD), testicular catalase and malondialdehyde (MDA) in G2 when compared with G1, whereas high-density lipoprotein cholesterol (HDL-C), serum testosterone, testicular 17 ketosteroid reductase (17 KSR), total thiol and glutathione-S-transferase (GST) data showed a significant decrease in G2 when compared with G1. Treatment with l-carnitine or/and vitamin E helps in improving the adverse effect of triton; also the histological changes confirm this finding. So the present study recommends all people to include l-carnitine and vitamin E in their diet to be protected against atherosclerosis.

Biochemical and histopathological studies of the PTU-induced hypothyroid rat kidney with reference to the ameliorating role of folic acid

Thyroid hormones (THs) are essential for growth and development of the kidney. Also TH influences glomerular filtration and tubular functions. Hypothyroidism negative influences kidney function indirectly by affecting the cardiovascular system and the renal blood flow, and directly by affecting glomerular filtration, tubular functions and the structure of the kidney. The purpose of this study was to evaluate changes in biochemical markers, oxidative stress parameter and histological changes in kidney of hypothyroid rats before and after treatment with folic acid. Hypothyroidism was induced for 6 weeks by the administration of propylthiouracil in drinking water. Urea and creatinine were measured to evaluate the changes in kidney function. Also malondialdehyde, nitrite, nitrate and other oxidative stress parameter were measured in serum and kidney tissue as indicators of oxidative damage. Kidney function and oxidative stress parameters in hypothyroid rats were significantly changed compared to those in control rats. Treatment with folic acid helps in improving the adverse effect of hypothyroidism; the histological study also confirms this finding.

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) +1858 C>T gene polymorphism in Egyptian cases with rheumatoid arthritis

BACKGROUND Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The gene encoding protein tyrosine phosphatase non-receptor type 22 (PTPN22) has been reported to be associated with RA in several populations. OBJECTIVES This work aimed at assessing the association of PTPN22 +1858 C>T gene polymorphism with the susceptibility, activity and severity of RA in Egyptian subjects. SUBJECTS AND METHODS This study included 112 unrelated RA patients who were compared to 122 healthy unrelated individuals taken from the same locality. For all subjects, DNA was genotyped for PTPN22 +1858 C>T (rs2476601) polymorphism using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS Cases showed significantly higher PTPN22 +1858 T allele carriage rate (CT+TT genotypes) compared to controls (34.8% vs. 8.2%, OR=5.98, 95% CI=2.81-12.73, p<0.001). Also the frequency of the PTPN22 +1858 T allele was significantly higher among cases compared to controls (18.7% vs. 4.5%, OR=4.89; 95% CI=2.45-9.76, p<0.001). Cases positive to the PTPN22 T allele (CT+TT genotypes) showed no significant difference from those with the CC genotype regarding clinical and immune parameters. Nonetheless, they showed a more functional disability presented in their significantly higher health assessment questionnaire (HAQ) score (p=0.04). CONCLUSIONS This study is a confirmatory evidence of the association of the PTPN22 +1858 T allele with susceptibility and functional disability of RA in Egyptian subjects.

Signal transducer and activator of transcription 4 (STAT4) G>T gene polymorphism in Egyptian cases with rheumatoid arthritis

BACKGROUND The gene encoding signal transducer and activator of transcription 4 (STAT4) has been reported to be associated with rheumatoid arthritis (RA) in several populations. This work aimed at assessing the association of STAT4 G>T gene polymorphism with the susceptibility, activity and functional disability of RA in Egyptian subjects. SUBJECTS AND METHODS This study included 112 unrelated RA Egyptian patients who were compared to 122 healthy unrelated individuals taken from the same locality. For all subjects, DNA was genotyped for STAT4 G>T (rs7574865) polymorphism using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS Cases showed a significantly higher frequency of the STAT4 T allele carriage (GT+TT genotypes) compared to controls (51.8% vs. 31.1%, OR = 2.37, 95% CI = 1.39-4.05, p = 0.001). Also the frequency of the STAT4 T allele was significantly higher among cases compared to controls (30.4% vs. 16.8%, OR = 2.16, 95% CI = 1.39-3.35, p = 0.001). Cases positive to the STAT4 T allele (GT+TT genotypes) showed no significant difference compared to those with the GG genotype regarding their clinical and immune parameters. Nonetheless, they showed a more functional disability presented in their significantly higher health assessment questionnaire (HAQ) score (p = 0.02). CONCLUSIONS This study gives an extra evidence to the association of the STAT4 T allele with the susceptibility and functional disability of RA.

Effects of phytate on thyroid gland of rats intoxicated with cadmium.

Cadmium (Cd) is one of the most dangerous occupational and environmental toxins. The objective of the present study is to examine the potential prophylactic effects of phytic acid (PA) on thyroid hormones of male rats intoxicated with Cd. The male albino rats were divided into five groups: group I (control) was fed with the basal diet, group II was intoxicated with Cd in drinking water, groups III, IV, and V were intoxicated with Cd in drinking water and fed with the diet containing 3.5, 7, and 10 g of PA/kg, respectively. The results indicated that the serum calcium, iron (Fe), and total Fe binding capacity levels and serum T3 and T4 in Cd-treated rats of group II were decreased when compared with the control group, while PA-administered groups with Cd showed a significant improvement when compared with the Cd-treated rats only. Serum thyroid stimulating hormone (TSH) level was significantly increased in Cd-treated rats compared with the control group, while the addition of PA in diet decreased the high levels of TSH. These results indicated a prophylactic effect of PA against Cd-induced toxicity in rats.

Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) + 49 A>G gene polymorphism in Egyptian cases with rheumatoid arthritis

BACKGROUND The gene encoding cytotoxic T lymphocyte associated antigen-4 (CTLA-4) has been reported to be associated with rheumatoid arthritis (RA) in several ethnic populations. The aim of this work is to assess the association of this polymorphism with the susceptibility, activity and functional disability of RA in Egyptian subjects. SUBJECTS AND METHODS This study included 112 unrelated RA Egyptian patients who were compared to 122 healthy controls from the same locality. For all subjects, DNA was genotyped for CTLA-4 +49 A>G (rs231775) polymorphism using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS The frequency of the CTLA-4 G allele was significantly higher among cases compared to controls (37.1% vs. 23.4%, OR=1.93; 95% CI=1.29-2.89, p=0.002). Also, the frequency of CTLA-4 +49 G allele carriage (AG+GG genotypes) was significantly higher among cases with RA compared to controls (61.6% vs. 41.8%, OR=2.23, 95% CI=1.32-3.77, p=0.003). Logistic regression analysis showed that cases positive to the G allele (GA+GG genotypes) had less frequency of rheumatoid deformities and also a lower DAS28-CRP score, yet with a higher visual analogue scale (VAS) i.e. more functional disability than other cases. CONCLUSIONS CTLA-4 +49 G allele carriage was associated with increased susceptibility and functional disability of RA in Egyptian patients.

Ameliorating Role of Folic Acid in Eltroxine Induced Hyperthyroid and Oxidative Stress in Rat Cortex, Hypothalamus and Hippocampus

Normal brain development requires the presence of thyroid hormones (TH). The present study aimed to declare the effect of hyperthyroidism on oxidative stress parameters in brain tissues (cortex, hypothalamus and hippocampus) and the role of folic acid supplementation in treatment. Thirty adult rats were divided into 5 groups (Group 1, Control; Group 2, Folic acid; Group 3, Hyperthyroid; Group 4, Co-treated hyperthyroid with folic acid; Group 5, Post treated hyperthyroid with folic acid). The current results showed a significant increase in the concentrations of T3 & T4 in hyperthyroid rats when compared with control group. In contrast, TSH showed a significant decrease in hyperthyroid rats when compared with the control group. Calcium was significantly increased in hyperthyroid group when compared with control group. Catalase and MDA were increased, while total protein in brain tissues was decreased in hyperthyroid rats (G3) when compared with control group. Total thiol in brain tissues showed a significant decrease in hyperthyroid group when compared with control group. Treatment with folic acid showed enhancement in oxidative stress parameters in post treated group more than co treated group.