الفهرس 
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Abstract
Chlorpyrifos (CPF) is known to induce acute and chronic neurotoxicity in people and animals primarily by inhibiting cholinesterase (AChE) activity. Besides causing in vivo toxicity by AChE inhibition, CPF may also induce other activities within exposed cells. Consequently, the current research has focused on identifying chlorpyrifos toxicity independent of its effect on AChE inhibition. The previous in vitro and in vivo studies showed that CPF at moderate concentrations induced organs toxicity, inflammation, oxidative stress, disturbed neurotransmission. Moreover, CPF and its metabolite chlorpyrifos oxon were able to induce apoptosis in several types of cells.
So the present study aims to evaluate the bioactive components of cactus and papaya fruit juices. Moreover to determine their effects on biological and biochemical parameters as well as microscopic examination on the alleviation of brain, liver, kidneys and testes cytotoxicity induced by chlorpyrifos in rats.
The present work included two parts:
1- The first part included the extraction of cactus and papaya fruit juices and determination of bioactive components of juices by GC-MS analysis. The results of analysis showed that phenolic compounds
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identified in cactus juice, the most abundant was caffeic acid with respectively 9.8 % of plant material. In terms of flavonoid composition isorhamnetin derivatives was the major component, it accounted for 24.6 %, quercetin derivatives for 24.4:; kaempferol derivatives for 13.1 % and rutin derivatives accounted for 6.7:. While papaya juice analysis showed that papaya fruits contain phenolic and flavonoid compounds (caffeic acid 16:, rutin
5: and quercetin 13:). Quercetin was the most abundant phenolics and only traces of gallic and protocatechuic acids conjugates were found.
2- The second part included the biological experiment to evaluate the effects of oral administration of cactus and/or papaya juices included: 64 healthy adult male albino rats Sprague- Dawley strain with weight range 184-244 g, fed on the balanced diet throughout the experimental period. Rats were divided into 5 groups each of 12 rats. First group was left as control group. Second group was given CPF (6 mg/kg b.wt.). Other groups were given CPF dose daily and treated as following: Third group was given cactus juice 24 ml/kg b.wt. Fourth group was given papaya juice 24 ml/kg b.wt. And fifth group was given cactus and papaya juices mixture 24 ml/kg b.wt. All doses were orally administered daily for 28 successive days.
The experimental results were as following:
1- Biological parameters show the following results:
5- The daily administration of CPF caused increased food intake and decreased body weight gain by 4.76: and 34.52:, respectively as compared with healthy group.
6- The relative organs weights also affected as following, CPF daily administration caused increased in relative brain, liver, kidneys and testes weights by 17.19:, 46.15:, 7.69: and 24.24:,
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respectively as compared with healthy group. While daily treatment with papaya juice caused decrement by 5.33: for relative brain weight while cactus and mixture juices caused no significant change in relative brain weight. Moreover, for relative liver and kidneys weights, cactus juice caused decrement by 9.71: and 14.65:; papaya juice caused decrement by 15.33 and 9.57; and mixture juices caused decrement by 25.4 and 12.86:, respectively as compared by CPF group. In addition, treatments with the juices not cause any significant improvement in relative testes weight when compared with CPF group.
2- Biochemical measurements involved the following sections:
Evaluation of organs (brain, liver, kidney and testes) functions as following:
o The results showed that daily administration of CPF caused decrement in AChE activity and dopamine level by 24.4: and 45.2 %; and increment in epinephrine and norepinephrine levels by 149.1:
and 146.17:, respectively as compared by healthy group. On the other hand, treatment with juices caused improvement as following; cactus juice caused increment in AChE activity and dopamine level by 38.99: and 64.14 % and decrement in epinephrine and norepinephrine levels by 32.77 and 21.25:, respectively as compared by CPF group; papaya juice caused increment in AChE activity and dopamine level by 29.19: and 144.42: and decrement in epinephrine and norepinephrine levels by 32.45: and 33.88:, respectively as compared by CPF group; cactus and papaya mixture juice caused increment in AChE activity and dopamine level by 31.96 and 153.16 % and decrement in epinephrine and norepinephrine levels by 6.76 and 16.46:, respectively as compared with CPF group.
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o The results showed that daily administration of CPF caused increment in ALT and AST levels by 154.34: and 152.2:, respectively as compared with healthy group. Moreover, treatment with juices caused improvement as following; cactus juice caused decrement in ALT and AST levels by 51.95 and 58.36:, respectively as compared with CPF group; papaya juice caused decrement in ALT and AST levels by 54.45 and 55.48:, respectively as compared by CPF group; cactus and papaya mixture juice caused decrement in ALT and AST levels by 49.32
and 55.4:, respectively as compared by CPF group.
o The results showed that daily administration of CPF caused increment in creatinine and urea levels by 11.73: and 24.35:, respectively as compared with healthy group. In addition, treatment with juices caused improvement as following; cactus juice caused decrement in creatinine and urea levels by 7.18 and 15.19:, respectively as compared with CPF group; papaya juice caused decrement in creatinine and urea levels by 3.31and 17.27 %, respectively as compared with CPF group; cactus and papaya mixture juice caused decrement in creatinine and urea levels by 4.97 and 17.23 %, respectively as compared with CPF group.
o The results of fertility biomarkers included semen analysis showed that CPF administration affect sperm motility, count and normality by 24.44, 32.26
and 55.56 %, respectively as compared with healthy group; and decrement in serum testosterone and lutelizing hormone and increment in follicle stimulating hormone levels by 84.4, 75.3 and 176.7:, respectively as compared with healthy group. On the other hand, treatment with cactus and /or papaya juices cause 24.44% improvement for motility in all treated groups, 59.5 %, 84.9 %and 54 % improvement for count and 244 %, 175 % and 212.5
% improvement for morphology as compared with
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CPF group, respectively. On the other hand, treatment with juices caused increment in serum testosterone and lutelizing hormone and decrement in follicle stimulating hormone levels as following; cactus juice caused improvement by 54.45, 76.72 and 54.6:, respectively as compared by CPF group; papaya juice caused improvement by 458.11, 142.59 and 32.53:, respectively as compared by CPF group; cactus and papaya mixture juice caused improvement by 516.21,
84.17 and 39.76:, respectively as compared with CPF group.
The results of enzymes of detoxification process showed that daily CPF administration increased serum cytochrome P454 and paraoxonase1 activities by 141.7 and 15.17: as compared with the healthy group. While, treatment caused improvement as following: cactus juice decreased cytochrome P454
activity by 6.6: and increased paraoxonase-1
activity by 28.41:; papaya juice decreased cytochrome P454 activity by 14.47: and paraoxonase-1 activity by 3.77:; cactus and papaya mixture juice decreased cytochrome P454 activity by 1.43: and increased paraoxonase-1 activity by 2.28: as compared with CPF group.
The results of inflammatory markers showed that daily CPF administration increased TNF-α and decreased IL-6 by 653.3 and 93.13:, respectively as compared with healthy group. On the other hand, treatment caused improvement as following: cactus juice decreased TNF-α by 59.46: and increased IL-6
by 16.95 % as compared with CPF group; papaya juice decreased TNF-α by 83.53: and increased IL-6
by 64.17 %; cactus and papaya mixture juice decreased TNF-α by 75.53: and increased IL-6 by 21.19% as compared by CPF group.
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The results of oxidative stress and antioxidant markers showed that daily CPF administration increased serum MDA, NO levels and CAT activity by 131.5 %, 346.6: and 196.4 %, respectively as compared with healthy group. On the other hand, treatment caused improvement as following: cactus juice decreased serum MDA, NO levels and CAT activity by 48.59, 65.48: and 4.42:, respectively; papaya juice decreased serum MDA, NO levels and CAT activity by 31.64:, 54.34: and 42.65:, respectively; cactus and papaya mixture juice decreased serum MDA, and NO levels and CAT activity by 46.41:, 65.9: and 24.77:, respectively as compared with CPF group.
The results of DNA fragmentation in tissues of brain, liver, kidneys and testes showed that daily CPF administration increased percentage of DNA fragmentation in these tissues by 88.78, 1284.6,
957.7 and 1446.7:, respectively as compared with healthy group. While, treatment caused improvement as following: cactus juice decreased DNA fragmentation in these tissues by 78.29, 87.25,
81.91 and 84.94:, respectively; papaya juice decreased DNA fragmentation in these tissues by 82.13, 84.84, 84.77 and 85.39:, respectively; cactus and papaya mixture juice decreased DNA fragmentation in these tissues by 88.78, 86.21, 82.4
and 87.68:, respectively as compared with CPF group.
The results of apoptosis marker (Caspase 3
level) in tissues of brain, liver, kidneys and testes showed that daily CPF administration increased caspase- 3 level in these tissues by 365.5, 327.1,
271.4 and 241.69:, respectively as compared with healthy group. While, treatment caused improvement as following: cactus juice decreased caspase 3 level in these tissues by 68.44, 54.63,
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53.97 and 42.89:, respectively; papaya juice decreased caspase 3 level in these tissues by 68.55,
64.56, 51.24 and 53.48:, respectively; cactus and papaya mixture juice decreased caspase 3 level in these tissues by 74.4, 54.53, 39.58 and 48.38:, respectively as compared with CPF group.
3- Microscopic examination
7- The results of microscopic examination for brain, liver, kidney and testes tissues showed that daily CPF administration caused impairment in these tissues however treatment with cactus and/or papaya juices protect these tissues against CPF detrimental effect.