Urtica pilulifera leaves extract mitigates cadmium induced hepatotoxicity via modulation of antioxidants, inflammatory markers and Nrf-2 signaling in mice.

Introduction: Cadmium (Cd) is a harmful heavy metal that results in many toxic issues. Urtica pilulifera showed potential pharmaceutical applications. This study investigated the possible ameliorative mechanism of Urtica pilulifera leaves extract (UPLE) against hepatotoxicity induced by cadmium chloride (CdCl2) in mice. Methods: In vitro phytochemical screening and the metal-chelating activity of UPLE were ascertained. Four groups of forty male mice were used (n = 10) as follows; Group 1 (G1) was a negative control. G2 was injected i.p., with UPLE (100 mg/kg b. wt) daily. G3 was injected i.p., with Cd (5 mg/kg b. wt) daily. G4 was injected with Cd as in G3 and with UPLE as in G2. On day 11, the body weight changes were evaluated, blood, and serum samples were collected for hematological and biochemical assessments. Liver tissues were used for biochemical, molecular, and histopathological investigations. Results: The results showed that UPLE contains promising secondary metabolites that considerably lessen the negative effects of Cd on liver. Furthermore, UPLE inhibited oxidative stress and inflammation; restored antioxidant molecules; and promoted nuclear-related factor-2 (Nrf-2) expression. Also, UPLE improved the histopathological alterations induced by Cd. Discussion: This study explored the beneficial role of UPLE treatment in Cd-induced liver injury through enhancing Nrf-2 signaling and antioxidant enzyme gene expression in the liver of mice. Therefore, UPLE could have valuable implications against hepatotoxicity induced by environmental cadmium exposure. Which can be used as a chelating agent against Cd.

A new cirrhotic animal protocol combining carbon tetrachloride with methotrexate to address limitations of the currently used chemical-induced models.

Background: Chemically induced cirrhotic animal models are commonly used. However, they have limitations such as high mortalities and low yield of cirrhotic animals that limit their uses. Aims: To overcome limitations of the chemically induced cirrhotic animal model via combined administration of methotrexate (MTX) with CCl4 and decrease their commonly used doses depending on the proposed synergetic cirrhotic effect. Methods: Rats were divided into six groups: normal (4 weeks), normal (8 weeks), MTX, CCl4 (4 weeks), CCl4 (8 weeks), and MTX + CCl4 (4 weeks) groups. Animals' hepatic morphology and histopathological characterization were explored. Hepatic Bcl2 and NF-κB-p65 tissue contents were determined using the immunostaining technique, and hepatic tissue damage, oxidative status, and inflammatory status biochemical parameters were determined. Results: CCl4 + MTX combined administration produced prominent cirrhotic liver changes, further confirmed by a substantial increase in oxidative stress and inflammatory parameters, whereas mortalities were significantly lower than in other treated groups. Conclusion: The present study introduced a new model that can significantly improve the major limitations of chemically induced cirrhotic animal models with new pathological features that mimic human cirrhosis. Compared to other chemically induced methods, the present model can save time, cost, and animal suffering.

Genetic influence of vitamin D receptor gene polymorphisms on osteoporosis risk.

OBJECTIVE: Osteoporosis is the most common type of bone disorder characterized by low bone mineral density (BMD). It is a multifactorial disease and caused by the interaction of environmental and genetic factors. It has been reported that mutations in the vitamin D receptor (VDR) gene highly affect the metabolism of minerals, which reduces bone density. Therefore, this study aimed to determine the association of VDR gene polymorphisms TaqI (rs731236) and ApaI (rs7975232) with osteoporosis risk in the Saudi population. METHODS: This case-control study involved 73 individuals with osteoporosis and 73 healthy controls in Jeddah, KSA. DNA extracted from peripheral blood was used to determine the genotypes and allele frequencies of VDR variants by polymerase chain reaction-restriction fragment length polymorphisms. Osteoporosis was confirmed by measuring BMD using dual-energy X-ray absorptiometry. The results were interpreted using the Hardy-Weinberg equilibrium assumption with P < 0.05 considered as significant. RESULTS: A significant increase in the genotype frequencies of the ApaI (Aa) and (aa) was observed among osteoporotic patients compared to controls (P = 0.002 and P < 0.0001, respectively). Only the homozygous (tt) genotype of TaqI was significantly higher in those with osteoporosis than in the controls (P = 0.001). The minor "a" allele of ApaI and the "t" allele of TaqI were significantly more common in the patients as compared to controls (P < 0.0001 and P = 0.01, respectively). CONCLUSION: VDR polymorphisms ApaI and TaqI were found to be significantly determinant risk factors for osteoporosis progression in the Saudi population.

Serum concentrations of pesticides including organophosphates, pyrethroids and neonicotinoids in a population with osteoarthritis in Saudi Arabia.

Human exposure to pesticides is widespread and has received much attention in recent years because of its link to adverse health outcomes. Measurement of urinary concentrations of pesticides and their metabolites is often used in the assessment of body burdens of these chemicals. However, pesticides and their metabolites can be present in blood circulatory system, although little is known on serum levels of pesticides. In this study, we aimed to examine the occurrence and profile of four organophosphate (OP), five pyrethroid (PYR) insecticides, two phenoxy acid (PA) herbicides, 14 neonicotinoid (neonic) insecticides and six dialkylphosphate metabolites in serum from 25 individuals diagnosed with osteoarthritis in Jeddah, Saudi Arabia. 2-Isopropyl-4-methyl-6-hydroxypyrimidine (IMPY), 3,5,6-trichloro-2-pyridinol (TCPY), 2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid, 3-phenoxybenzoic acid, N-desmethyl acetamiprid, dimethylphosphate (DMP) and dimethylthiophosphate (DMTP) were detected in ≥80% of the serum samples analyzed. Metabolites of OPs, DMTP (median concentration: 2.14 ng/mL), DMP (1.04 ng/mL) and TCPY (0.84 ng/mL), collectively accounted for 67-83% of the total serum pesticide concentrations. Serum concentrations of pesticides were similar to or lower than those reported in urine. Our preliminary evidence suggests that serum can be used as a matrix for the assessment of exposure to OPs, PYRs, PAs and neonics.

Serum concentrations of perfluoroalkyl substances and their association with osteoporosis in a population in Jeddah, Saudi Arabia.

Human exposure to poly- and perfluoroalkyl substances (PFASs) is widespread and has received considerable attention in recent years due to their link with adverse health outcomes, including bone health. Nevertheless, no earlier studies have reported serum PFAS concentrations, and their association with incident osteoporosis in populations in Saudi Arabia. In this clinical case-control study, serum samples collected from 208 individuals (n = 100 cases and n = 108 controls) aged 40-89 years from Jeddah, Saudi Arabia, were analyzed for 17 PFASs. Unconditional logistic regression was used to calculate odds ratios (ORs) for association between serum PFAS concentrations and osteoporosis, stratified by gender, age, serum calcium and vitamin D, previous history of fractures and thyroid disorders. Perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorobutanoic acid (PFBA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), perfluoro-n-pentanoic acid (PFPeA) and perfluoroundecanoic acid (PFUnDA) were detected in >80% of serum samples analyzed. PFOS (overall median concentration: 5.08 ng/mL), PFHxS (1.49 ng/mL), PFOA (1.33 ng/mL) and PFNA (0.55 ng/mL) accounted for 94% and 80% of the total serum PFASs concentrations in cases and controls, respectively. Serum PFOA, PFNA and PFUnDA concentrations increased with age in Saudi women. Results from the crude models showed that individuals in the 2nd, 3rd and 4th quartiles of serum PFAS concentrations had 2.3-96-fold increase in odds of diagnosis for osteoporosis compared with those in the 1st quartile (rank order: PFUnDA > PFOA > PFNA > PFOS > PFHxS). Our results suggest that exposure to PFOA, PFOS, PFNA, PFHxS and PFUnDA was associated with osteoporosis in this sample of adult Saudi population.