METHODS: A cross-sectional study was conducted among male farmers from 3 different communities in Sabah, Malaysia. A total of 152 farmers participated in this study of whom 62 farmers had been exposed to either paraquat or malathion or both to varying extents. Questionnaires were designed to record a history of pesticides exposure and other potential risk factors among farmers. All semen samples were collected, processed and analyzed by qualified personnel based on WHO guidelines. Volume, pH, sperm concentration, motility, morphology and WBC count were examined and recorded. The association between pesticide exposure and semen parameters was highly significant.
RESULTS: The mean values of volume, pH, sperm concentration, motility, and WBC count were significantly less in the exposed group than in compared with the non-exposed group, with p<0.005. Those who were exposed to pesticides had greater risk of having abnormal semen parameters than those in with the non exposed group, with p values of less than 0.05. The comparison between semen qualities such as lower sperm count, motility and higher percentage of sperm abnormality of those exposed to different types of pesticides (paraquat and malathion) showed no significant differences.
CONCLUSION: The results showed a significant decline in semen quality with a decline in sperm count, motility and higher percent of teratospermia among subjects with pesticide exposure, and those who were exposed to pesticides had significantly 3 to 9 times greater risk of having abnormal semen parameters.
Methods: Human neuroblastoma cells SH-SY5Y (as a neuronal model) and human glioblastoma cells T98G (as an astrocytic model), were treated with 100-500 µM PA, oleic acid (OA) or lauric acid (LA) for 24 h or 48 h, and their cell viability was assessed by 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of stable overexpression of γ-synuclein (γ-syn), a neuronal protein recently recognized as a novel regulator of lipid handling in adipocytes, and transient overexpression of Parkinson's disease (PD) α-synuclein [α-syn; wild-type (wt) and its pathogenic mutants A53T, A30P and E46K] in SH-SY5Y and T98G cells, were also evaluated. The effects of co-treatment of PA with paraquat (PQ), a Parkinsonian pesticide, and leptin, a hormone involved in the brain-adipose axis, were also assessed. Cell death mode and cell cycle were analyzed by Annexin V/PI flow cytometry. Reactive oxygen species (ROS) level was determined using 2',7'-dichlorofluorescien diacetate (DCFH-DA) assay and lipid peroxidation level was determined using thiobarbituric acid reactive substances (TBARS) assay.
Results: MTT assay revealed dose- and time-dependent PA cytotoxicity on SH-SY5Y and T98G cells, but not OA and LA. The cytotoxicity was significantly lower in SH-SY5Y-γ-syn cells, while transient overexpression of wt α-syn or its PD mutants (A30P and E46K, but not A53T) modestly (but still significantly) rescued the cytotoxicity of PA in SH-SY5Y and T98G cells. Co-treatment of increasing concentrations of PQ exacerbated PA's neurotoxicity. Pre-treatment of leptin, an anti-apoptotic adipokine, did not successfully rescue SH-SY5Y cells from PA-induced cytotoxicity-suggesting a mechanism of PA-induced leptin resistance. Annexin V/PI flow cytometry analysis revealed PA-induced increase in percentages of cells in annexin V-positive/PI-negative quadrant (early apoptosis) and subG0-G1 fraction, accompanied by a decrease in G2-M phase cells. The PA-induced ROS production and lipid peroxidation was at greater extent in T98G as compared to that in SH-SY5Y.
Discussion: In conclusion, PA induces apoptosis by increasing oxidative stress in neurons and astrocytes. Taken together, the results suggest that HFD may cause neuronal and astrocytic damage, which indirectly proposes that CNS pathologies involving neuroinflammation and reactive gliosis could be prevented via the diet regimen.