الفهرس 
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Abstract
The present study aims to assess the toxic effect of Calotropis procera latex and ethanolic extract of leaves in comparison with abamectin administration on liver, kidney, heart and testis of male albino rats. To achieve this aim, serum markers of organ function, organ oxidative stress and antioxidant defense system, pro-inflammatory cytokines, anti-inflammatory cytokines and histopathological changes were investigated.
LD50 of latex was determined through oral administration of latex in gradual increasing doses (0.4, 0.8, 1.2, 1.6, 2, 2.4, 2.8, 3.2 ml/ kg b.w.) for 8 groups each of 5 male albino mice. After 72 hours of administration, the number of dead animals in each group and LD50 was calculated using some equations.
The albino rats used in this study were allocated into 7 groups. group 1 was orally administered 1% carboxy methyl cellulose (CMC) for 4 weeks and 8 weeks and regarded as control groups. The second group was orally treated with 1/20 of LD50 of Calotropis procera latex (66µl/kg b.wt) for 4 weeks and 8 weeks. The third group was orally treated with 1/10 of LD50 of C. procera latex (132µl/kg b.wt) for 4 weeks and 8 weeks. The fourth group was orally administered 1/20 of LD50 of ethanolic extract of C. procera leaves (4.78 mg/kg b.wt) for 4 weeks and 8 weeks. The fifth group was administered orally with 1/10 of LD50 of ethanolic extract of C. procera leaves (9.56 mg/kg b.wt) for 4 weeks and 8 weeks. The sixth group was orally administered with 1/20 of LD50 of abamectin (vertimec 1.8% EC) (0.44 mg /kg b.wt) for 4 weeks and 8 weeks. The seventh group was orally administered with 1/10 of LD50 of abamectin (vertimec 1.8% EC) (0.87 mg/kg b.wt) for 4 weeks and 8 weeks.
After each period of treatments (4 weeks and 8 weeks), one testis, part of liver, part of heart, and one kidney were taken for studying the histopathological changes. Part of liver was kept in ice for molecular studies. Blood samples were obtained for determination of liver function (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities and albumin and bilirubin levels), heart function (aspartate amino transferase (AST), lactate dehydrogenase (LDH) and creatinine kinase-MB (CK-MB)), kidney function (urea, uric acid and creatinine), male sex hormones (testosterone, FSH and LH), serum TNF-α and interlukin-4 (IL-4). Moreover, part of heart heart, one kidney, one testis, and liver were taken for quantitative determination of parameters of oxidative stress and antioxidant defense system.
The obtained data of the above mentioned investigations revealed the following:
(1) Treatments with latex and ethanolic extract of leaves of C. procera and abamectin for 4 and 8 weeks induced marked increase in ALT, AST and ALP activities and total bilirubin level and decreased serum albumin level. The most adverse effect on ALT activity was achieved after treatment with 1/10 of LD50 abamectin followed by 1/10 LD50 ethanolic extract. Treatment with 1/10 latex achieved the most potent increase in ALP activity followed by abamectin and the extract.
(2) Regarding the kidney function parameters, the recorded concentrations of serum urea, uric acid and creatinine were significantly increased as a result of latex, ethanolic extract and abamectin administration. Increasing dose induced more elevations in concentrations of these parameters but increasing time has no effect on creatinine and uric acid concentrations.
(3) Elevation in the heart function parameters (serum CK-MB, AST and LDH activities) occurred after administration of latex, extract and abamectin. This elevation was more progressed with increasing the dose.
(4) Administration of latex, extract of C. procera and abamectin induced adverse effects on male fertility by decreasing the levels of sex hormones significantly.
(5) In the treated rats, there was disturbance in the oxidant/ antioxidant status indicated by increasing in the lipid peroxidation in all treated groups in different organs and this increase is dose dependent. Significant decrease in glutathione content and antioxidant enzymes (GPx, GST and SOD) activities occurred and this decrease is dose dependent.
(6) With regard to serum TNF-α, the tested plant and abamectin elevated the serum level of the inflammatory cytokine (TNF-α) and this increase is dose dependent. On the other hand, administration of the plant and the biocide induced marked decrease in the values of the anti-inflammatory cytokine (IL-4) after 4 weeks. This decrease is dose dependent but prolongation of period of the level returned to normal with extract and abamectin treatments.
(7) Latex, ethanolic extract and abamectin administrations impaired the histological architecture and integrity of liver, kidney, heart and testis.
(8) Regarding gene expression, there were marked activations in the P53 and NF-ϰB mRNA expression in treated rats. On the other hand, significant suppression of the anti-apoptotic gene Bcl2 expression occurred.
In conclusion, latex and ethanolic extract of leaves of C. procera and abamectin could induce marked toxicity in different organs via induction of oxidative stress, inflammation and apoptosis.