The role of oxidative stress in antipsychotics induced ovarian toxicity

This study tested the hypothesis that oxidative stress could be an underlying mechanism for APs-induced ovarian cytotoxicity and reproductive dysfunction. Rat ovarian theca interstitial cells (TICs) were isolated and treated with four APs [chlorpromazine (CPZ), haloperidol (HAL), risperidone (RIS) and clozapine (CLZ)]. MTT assay was used to test the effects of these antipsychotics on TICs viability and to estimate their 50% inhibitory concentrations (IC50s). The effects of APs (IC50s and 1 μM concentrations) on the activities of caspases-3, -8 and -9, reactive oxygen species (ROS) production, total intracellular glutathione and lipid peroxidation (LPO) in TICs were assessed. The effect of antioxidants (reduced glutathione (GSH) and quercetin) on the APs-induced cytotoxicity on TICs was investigated. MTT assay showed all APs to reduce TICs viability. CPZ, HAL and CLZ significantly increased the activity of caspases-3, -8 and -9 (P < 0.0001, < 0.0001 and < 0.01, respectively). All APs at IC50s significantly (P < 0.0001) increased ROS production, decreased total intracellular glutathione and increased LPO. MTT assay in the presence of antioxidants (reduced GSH (5 mM) or quercetin (50 mM)) showed each antioxidant to significantly inhibit the effects of APs at their IC50s on TICs viability. In conclusion, oxidative stress seems to be a possible mechanism for APs-induced ovarian and reproductive toxicity

Therapeutic concentrations of antidepressants inhibit pancreatic beta-cell function via mitochondrial complex inhibition

Diabetes mellitus risk is increased by prolonged usage of antidepressants (ADs). Although various mechanisms are suggested for their diabetogenic potential, whether a direct effect of ADs on pancreatic β-cells is involved is unclear. We examined this idea for 3 ADs: paroxetine, clomipramine and, with particular emphasis, fluoxetine, on insulin secretion, mitochondrial function, cellular bioenergetics, KATP channel activity, and caspase activity in murine and human cell-line models of pancreatic β-cells. Metabolic assays showed that these ADs decreased the redox, oxidative respiration, and energetic potential of β-cells in a time and concentration dependent manner, even at a concentration of 100 nM, well within the therapeutic window. These effects were related to inhibition of mitochondrial complex I and III. Consistent with impaired mitochondrial function, lactate output was increased and insulin secretion decreased. Neither fluoxetine, antimycin nor rotenone could reactivate KATP channel activity blocked by glucose unlike the mitochondrial uncoupler, FCCP. Chronic, but not acute, AD increased oxidative stress and activated caspases, 3, 8, and 9. A close agreement was found for the rates of oxidative respiration, lactate output and modulation of KATP channel activity in MIN6 cells with those of primary murine cells; data that supports MIN6 as a valid model to study beta-cell bioenergetics. To conclude, paroxetine, clomipramine and fluoxetine were all cytotoxic at therapeutic concentrations on pancreatic beta-cells; an action suggested to arise by inhibition of mitochondrial bioenergetics, oxidative stress and induction of apoptosis. These actions help explain the diabetogenic potential of these ADs in humans

ABCB1 variants C3435T and T129C are not associated with colorectal cancer risk

Background: Colorectal cancer (CRC) is one of the most prevalent cancers in Saudi Arabia that is highly characterized with poor survival rate and advanced metastasis. Many studies contribute this poor outcome to the expression of ABC transporters on the surface of cancer cells. Objectives: In this study, two ABCB1 variants, C3435T and T129C, were examined to evaluate their contribution to CRC risk. Methods: 125 subjects (62 CRC patients and 63 healthy controls) were involved. The DNA was isolated and analyzed with PCR-RFLP to determine the different genotypes. The hardy-Weinberg equilibrium was performed to determine genotype distribution and allele frequencies. Fisher\u2019s exact test (two-tailed) was used to compare allele frequencies between patients and control subjects. Results: The study showed that for SNP C3435T, the population of both CRC patients and controls were out of Hardy-Weinberg equilibrium. Genotype distribution for CRC patients was (Goodness of fit \u3c72 = 20, df= 1, P 640.05), whereas, for the controls the genotype distribution was (Goodness of fit \u3c72 = 21, df =1, P 640.05). For SNP T129C, all subjects showed normal (TT) genotype. Conclusion: There was no significant association between ABCB1 3435C&gt;T and 129T&gt;C polymorphisms with CRC risk

Comparative Study of the Antioxidant Activity of Two Popular Green Tea Beverages Available in the Local Market of Saudi Arabia

Abstract Antioxidants have numerous applications due to their multiple roles in diminishing harmful effects of oxidative stress. The objective of this work was to highlight the importance of green tea by evaluating the antioxidant activity of the most popular green tea brands in Saudi Arabia, Lipton and Rabea. To our knowledge, no studies have so far been done to estimate the antioxidant activity of these brands. To determine the antioxidant activities of these two brands, 10 mg/ml of each brand was extracted and their total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, hydrogen peroxide scavenging activity, ferric reducing power and ferrous ion chelating effect were measured. The TPC of Lipton tea was 678.7 µg of gallic acid equivalents (GAE)/10mg, whereas in Rabea tea, the TPC was 647.1 µg GAE/10mg. The presence study indicated that there were no significant differences in total phenolic contents and the percentage inhibition as shown in DPPH and H 2 O 2 assays among Lipton and Rabea green teas. Moreover, it was found that all assays have exhibited high antioxidant activity in both green teas. In conclusion, our study showed evidence for evenness and stability of the antioxidant activity of the two commercial green teas available in the markets of Saudi Arabia. Continued researches are needed to further the current knowledge on the health-promoting effects of this popular beverage using different supplements by different mechanisms

Understanding renal posttransplantation anemia in the pediatric population

Advances in renal transplantation management have proven to be beneficial in improving graft and patient survival. One of the properties of a well-functioning renal allograft is the secretion of adequate amounts of the hormone erythropoietin to stimulate erythropoiesis. Posttransplantation anemia (PTA) may occur at any point in time following transplantation, and the cause is multifactoral. Much of our understanding of PTA is based on studies of adult transplant recipients. The limited number of studies that have been reported on pediatric renal transplant patients appear to indicate that PTA is prevalent in this patient population. Erythropoietin deficiency or resistance is commonly associated with iron deficiency. An understanding of the risk factors, pathophysiology and management of PTA in the pediatric renal transplant population may provide guidelines for clinicians and researchers in the pursuit of larger prospective randomized control studies aimed at improving our limited knowledge of PTA. Recognition of PTA through regular screening and evaluation of the multiple factors that may contribute to its development are recommended after transplantation

Bioaccumulation and ecotoxicity of carbon nanotubes

Carbon nanotubes (CNT) have numerous industrial applications and may be released to the environment. In the aquatic environment, pristine or functionalized CNT have different dispersion behavior, potentially leading to different risks of exposure along the water column. Data included in this review indicate that CNT do not cross biological barriers readily. When internalized, only a minimal fraction of CNT translocate into organism body compartments. The reported CNT toxicity depends on exposure conditions, model organism, CNT-type, dispersion state and concentration. In the ecotoxicological tests, the aquatic organisms were generally found to be more sensitive than terrestrial organisms. Invertebrates were more sensitive than vertebrates. Single-walled CNT were found to be more toxic than double-/multi-walled CNT. Generally, the effect concentrations documented in literature were above current modeled average environmental concentrations. Measurement data are needed for estimation of environmental no-effect concentrations. Future studies with benchmark materials are needed to generate comparable results. Studies have to include better characterization of the starting materials, of the dispersions and of the biological fate, to obtain better knowledge of the exposure/effect relationships

Genetic Variants in the Mitochondrial Thymidylate Biosynthesis Pathway Increase Colorectal Cancer Risk

We assess the contributions of genetic variants for the enzymes involved in capecitabine metabolism to colorectal cancer (CRC) development risk. In this case-control study, DNA samples were collected from 66 patients (King Abdulaziz University Hospital) and 65 controls (King Fahad General Hospital) between April and November 2022 to be used in PCR-RFLP. The chi-square (χ2) test at a significance level of p ˂ 0.05 was used to estimate genotype and allele frequencies. The Lys27Gln variant of cytidine deaminase (CDA) showed a risk ratio (RR) of 1.47 for heterozygous (AC) carriers, with genotype distributions for patients (χ2 = 1.97) and controls (χ2 = 14.7). Homozygous (AA) Ala70Thr carriers demonstrated a three-fold higher risk, with genotype distributions for patients (χ2 = 3.85) and controls (χ2 = 4.23). Genotype distributions of the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T variant for patients were (χ2 = 22.43) and for controls were (χ2 = 0.07); for the MTHFR A1298C variant, they were (χ2 = 54.44) for patients and (χ2 = 4.58) for controls. Heterozygous (AC) carriers of the A1298C variant demonstrated highly significant protection against CRC development (RR = 0.2, p = 0.001), while a two-fold higher risk for CRC was estimated for homozygous genotype (CC) carriers. In conclusion, the heterozygous genotype of CDA Lys27Gln, the homozygous genotype of CDA Ala70Thr, and the homozygous genotype of MTHFR A1298C were associated with CRC development risk. The heterozygous genotype of MTHFR A1298C variant provided highly significant protection against CRC development. Further examinations using a larger population size are needed to reliably confirm our findings

Addition of evaporated milk alters antioxdant properties of most commonly consumed coffee in Saudi Arabia

Coffee is one of the most commonly consumed beverages worldwide. The aim of current study is to evaluate the effect of adding evaporated milk (full fat and low fat) on the antioxidant properties of coffee and to assess the possible alterations of polyphenols bioavailability when evaporated milk is added. To determine the effects of adding milk on the antioxidant activities of instant coffee, total polyphenols and flavonoids contents, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, hydrogen peroxide scavenging activity, ferric reducing power and ferrous ion chelating effect were determined. Total polyphenol and flavonoid contents were significantly higher (p<0.0001) in both coffee milk samples, coffee with full fat evaporated milk (CFEM) and coffee with low fat evaporated milk (CLEM), in comparison to pure coffee. Moreover, DPPH scavenging activity was significantly increased (p<0.001) in CFEM and CLEM whereas, hydrogen peroxide radical scavenging activity and ferric reducing power were significantly decreased (p<0.001) in CFEM and CLEM samples. In conclusion, our study showed that adding different concentrations of evaporated milk to instant coffee influences the bioavailability and efficacy of coffee antioxidants. This might be due to the presence of proteins and fats in milk