The correlation between Aflatoxin B1 and Placental Apoptosis in Pregnant women with Intrauterine Growth Restriction

Objective:To explore the effect of Aflatoxin B1 toxicity as a risk factor of intrauterine growth restriction (IUGR) and to determine the role of placental apoptotic indices in the pathogenesis of IUGR and their association with maternal risk factors including residency, working and exposure to smoking. Materials and Methods:A case-control study was done at Women Health Hospital; Assiut University, Egypt. Sixty pregnant women with asymmetrical IUGR and a control group of 40 normal pregnancies were selected. Maternal urine samples were obtained for Aflatoxin B1 level measurement by layer chromatography. Quantitative determination of human placental Bcl-2 and caspase-3 using a monoclonal antibody-based enzyme-linked immunosorbent assay kits were performed. Results:The results showed that aflatoxin B1 positive cases in the IUGR group had significantly higher placental caspase-3 and lower placental Bcl-2 concentrations than those which were aflatoxin B1 negative (p<0.01). The levels of placental apoptotic indices were higher in working women who lived in urban areas and those exposed to cigarette smoke than non-working women who lived in rural areas and non-smokers. Conclusions: Aflatoxin B1 may affect the fetal growth by increasing the placental apoptosis. These results may highlight the importance of aflatoxin B1 which may contribute to the complex etiology of IUGR. Placental apoptotic indices levels were significantly affected by maternal residence, working and exposure to smoking in pregnancies complicated with IUGR

Exposure to pesticide components causes recurrent pregnancy loss by increasing placental oxidative stress and apoptosis: a case–control study

Abstract We investigated the plasma levels of pesticides components namely polychlorinated biphenyls (PCBs), dieldrin, dichlorodiphenyldichloroethylene (DDE), ethion, malathion, and chlorpyrifos in recurrent pregnancy loss (RPL) cases, and tested their associations with placental oxidative stress (OS) biomarkers [nitric oxide (NO.), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and superoxide dismutase (SOD)] and with placental apoptotic/antiapoptotic indices (Bcl-2 and caspase-3), and evaluated their possible cut-off points to distinguish RPL cases. The study recruited 101 pregnant women divided into; G1 [n = 49, control, normal 1st-trimester pregnancy, normal obstetric history with at least one previous normal live birth], G2 [n = 26, cases with missed abortion (< 3 abortions) before 24 weeks of gestation], and G3 [n = 26, cases with missed abortion (≥ 3 abortions) before 24 weeks of gestation]. The plasma pesticide levels were analyzed by gas chromatography-mass spectrometry. Plasma human chorionic gonadotrophin (HCG), placental OS, Bcl-2, and caspase-3, were analyzed by their corresponding methods and kits. Plasma PCBs, DDE, dieldrin, and ethion levels were significantly higher in RPL cases than in normal pregnancies (p ≤ 0.001). These levels correlated positively with placental OS and apoptosis and negatively with plasma HCG levels. Also, these levels were reliable markers of risk to RPL. Malathion and chlorpyrifos were not detected in any of the study’s participants. Pesticides may be risk factors in cases of spontaneous RPL cases. They are associated with an increasing placental OS and placental apoptosis. Specific measures should be taken to decrease maternal exposure to these pollutants’ sources, especially in underdeveloped and developing countries

Amelioration of Diabetes-Induced Nephropathy by Loranthus regularis: Implication of Oxidative Stress, Inflammation and Hyperlipidaemia

In traditional Yemeni medicine, various preparations of Loranthus regularis (L. regularis), such as powder, decoctions and infusions are commonly used to treat diabetes, kidney stone formations and inflammation. In the present study, we evaluated the antinephrotoxic effects of L. regularis extract in experimentally-induced diabetes in male Wistar rats. A single dose (60 mg/kg/day) of Streptozotocin (STZ) was used to induce type 1 diabetes. Animals were then treated for four weeks with L. regularis extract (150 or 300 mg/kg/day) by oral gavage. Renal and blood samples were subsequently harvested. Several biochemical indices, oxidative stress and inflammatory markers were assessed. Additionally, histological alterations in the renal tissue were examined. Serum glucose levels were significantly (p &lt; 0.01) lowered while insulin levels were enhanced in L. regularis-treated diabetic animals. The increased renal markers in diabetic rats were decreased by L. regularis treatment. Serum elevated lipid profiles were markedly decreased by the plant extract. The serum and renal cytokines that were significantly increased (p &lt; 0.001) by STZ were diminished by L. regularis treatment. Finally, renal tissue antioxidant enzymatic activity was enhanced with L. regularis treatment. Taken together, the data here indicate that L. regularis possesses therapeutic ability to reduce the development of diabetic nephropathy (DN) by minimizing oxidative injury and inflammation

Thymoquinone, but Not Metformin, Protects against Gentamicin-Induced Nephrotoxicity and Renal Dysfunction in Rats

Background: Gentamicin (GM) is an antibiotic that is widely used to treat many Gram-negative bacteria, such as those involved in urinary tract infections. However, being nephrotoxic, GM dose adjustment and reno-protective elements must be concurrently administered with GM to minimize kidney damage. Oxidative stress plays a pivotal role in the pathogenesis of GM-induced nephrotoxicity. Thymoquinone (TQ) is a promising therapeutic substance, that is being extensively studied in many diseases, such as diabetes mellitus, cancer, hypertension, and others. The powerful antioxidant properties of TQ may greatly help in minimizing GM nephrotoxicity. Metformin (MF) is a well-known, clinically approved oral hypoglycaemic drug that has many other actions, including antioxidant properties. The aim of this work was to evaluate the possible antioxidant and reno-protective effects of TQ and metformin in GM-induced nephrotoxicity in the same model (rats) at the same time. In addition, we aimed to further understand the effects underlying GM-induced nephrotoxicity. Methods: Twenty male rats were randomly divided into four equal groups: the first group (control) received distilled water; the second group received GM only; the third group received concurrent oral TQ and GM; and the fourth group received concurrent oral MF and GM. After 4 weeks, renal function and histopathology, as well as levels of the oxidative markers glutathione peroxidase-1 (GLPX1), superoxide dismutase (SOD), and malondialdehyde (MDA) in the kidney tissues, were assessed. Results: Compared with the control group, and as expected, the GM-injected rats showed significant biochemical and histological changes denoting renal damage. Compared with GM-injected rats, the concurrent administration of TQ with GM significantly reduced the levels of serum creatinine, serum urea, and tissue MDA and significantly increased the levels of GLPX1 and SOD. Concurrent metformin administration with GM significantly increased the levels of both GLPX1 and SOD and significantly decreased the levels of tissue MDA but had no significant effect on serum creatinine and urea levels. Compared with GM-injected rats, the addition of either TQ or MF resulted in a reduction in endothelial proliferation and mesangial hypercellularity. Conclusions: Both TQ and MF effectively alleviated the oxidative stress in GM-induced nephrotoxicity in rats, with TQ but not MF producing a complete reno-protective effect. Further studies for evaluation of different reno-protective mechanisms of TQ should be conducted

Comparative Phytochemical Profile and Biological Activity of Four Major Medicinal Halophytes from Qassim Flora

Four halophytic plants, Lycium shawii, Anabasis articulata, Rumex vesicarius, and Zilla spinosa, growing in the central Qassim area, Saudi Arabia, were phytochemically and biologically investigated. Their hydroalcoholic extracts’ UPLC-ESIQ-TOF analyses demonstrated the presence of 44 compounds of phenolic acids, flavonoids, saponins, carbohydrates, and fatty acids chemical classes. Among all the plants’ extracts, L. shawii showed the highest quantities of total phenolics, and flavonoids contents (52.72 and 13.01 mg/gm of the gallic acid and quercetin equivalents, respectively), along with the antioxidant activity in the TAA (total antioxidant activity), FRAP (ferric reducing antioxidant power), and DPPH-SA (2,2-diphenyl-1-picryl-hydrazyl-scavenging activity) assays with 25.6, 56.68, and 19.76 mg/gm, respectively, as Trolox equivalents. The hydroalcoholic extract of the L. shawii also demonstrated the best chelating activity at 21.84 mg/gm EDTA equivalents. Among all the four halophytes, the hydroalcoholic extract of L. shawii exhibited the highest antiproliferative activity against MCF7 and K562 cell lines with IC50 values at 194.5 µg/mL and 464.9 µg/mL, respectively. The hydroalcoholic extract of A. articulata demonstrated better cytotoxic activity amongst all the tested plants’ extracts against the human pancreatic cancer cell lines (PANC1) with an IC50 value of 998.5 µg/mL. The L. shawii induced apoptosis in the MCF7 cell lines, and the percentage of the necrotic cells changed to 28.1% and 36.5% for the IC50 and double-IC50 values at 22.9% compared with the untreated groups. The hydroalcoholic extract of L. shawii showed substantial antibacterial activity against Bacillus cereus ATCC 10876 with a MIC value of 12.5 mg/mL. By contrast, the A. articulata and Z. spinosa exhibited antifungal activities against Aspergillus niger ATCC 6275 with MIC values at 12.5 and 50 mg/mL, respectively. These findings suggested that the L. shawii is a potential halophyte with remarkable biological properties, attributed to its contents of phenolics and flavonoid classes of compounds in its extract