THERAPEUTIC EFFICACY OF ALPHA LIPOIC ACID IN COMBINATION WITH SUCCIMER AGAINST LEAD-INDUCED OXIDATIVE STRESS, HEPATOTOXICITY AND NEPHROTOXICITY IN RATS التأثير العلاجي لحامض الألفاليبوک عند إضافته للسکسمر المضاد للجهد المؤکسد والتسمم الکبدي والکلوي للرصاص في الجرذان

Document Type : Original Article

Abstract

ABSTRACT:




Lead toxicity is a worldwide health problem due to continuous exposure of the population to lead in the environment especially workers in industries. It affects many body organs especially the liver and kidneys. The aim of this study is to investigate and compare the therapeutic potential of alpha lipoic acid (ALA) when it is administrated alone and in combination with succimer or dimercaptosuccinic acid (DMSA) against lead induced oxidative stress, hepatotoxicity and nephrotoxicity. Seventy five healthy male albino rats were used divided into 5 equal groups. Group (1) the control group was administrated distilled water orally for 6 weeks. Group (II) rats were given lead acetate (0.2%) in drinking water for 5 weeks and distilled water only orally during the 6th week . Group (III, IV and V) rats were given lead acetate (0.2%) in drinking water for 5 weeks followed by DMSA in a dose of 20 mg/kg body weigh/day intraperitoneally (i.p.) alone, ALA in a dose of 25 mg/kg body weigh/day (i.p.) alone and both drugs in combination during the 6th week only respectively. Rats were sacrificed after six weeks. Blood lead level, serum lipid peroxides (TBARS), serum total antioxidant (TAO) and serum nitric oxide (NO) levels were measured. Also Liver function tests (serum alkaline phosphatase, glutamic oxalacetic transaminase and glutamaic pyruvic transaminase) were measured. In addition, kidney function tests (serum urea, creatinine and uric acid) were done. Results showed an increase in the mean of blood lead level, increase serum TBARS levels, decrease serum TAO and NO levels and increase levels of liver and kidney function tests in lead treated group. Treatment with DMSA alone resulted in reduction of blood lead levels, improvement of serum NO level but not decrease serum TBARS level and moderate decrease in the elevated liver and kidney function test parameters. Rats treated with ALA alone showed no reduction in the elevated blood lead levels, but decreased serum TBARS and improved serum NO, TAO levels, liver and kidney function tests. Rats treated with DMSA and ALA concurrently showed decrease in blood lead levels, decrease serum TBARS, increase serum NO and TAO levels to near normal level and corrected liver and kidney function tests. In conclusion administration of ALA has beneficial effect as thiol-mediated antioxidant function when given to occupationally exposed workers to lead and during treatment of lead poisoning with DMSA as it increases its efficacy.
يعتبر التسمم بالرصاص مشکلة صحية في کل دول العالم لتأثيره على عديد من أجهزة الجسم وخاصة الکبد والکلى نتيجة تعرض الأهالي المستمر للرصاص في البيئة خاصة العمال في المصانع. تهدف هذه الدراسة لمعرفة ومقارنة التأثير العلاجي لحامض الألفاليبوک عند إعطائه بمفرده أو مع السکسمر المضاد للجهد المؤکسد والتسمم الکبدي والکلوي للرصاص في الجرذان البيضاء.
قد أجريت هذه الدراسة على 75 من ذکور الجرذان البيضاء البالغة السليمة التي قسمت إلى خمسة مجموعات (15 جرذ فى کل مجموعة)، المجموعة الأولى تم استخدامها کمجموعة ضابطة تم إعطائها الماء المقطر بالفم لمدة ستة أسابيع، المجموعة الثانية تم إعطائها خلات الرصاص المذابة في الماء المقطر لمدة خمسة أسابيع والماء المقطر بالفم في الأسبوع السادس، المجموعات الثالثة والرابعة والخامسة تم إعطائها خلات الرصاص المذابة في الماء المقطر لمدة خمسة أسابيع ثم إعطائها على التوالى  في الأسبوع السادس إما السکسمر بجرعة 20مجم/کجم بمفرده داخل التجويف البريتونى وحامض الألفاليبوک بمفرده بجرعة 25 مجم/کجم داخل التجويف البريتونى وکلاً من حامض الألفاليبوک والسکسمر بجرعة 25، 20 مجم/جم داخل التجويف البريتونى. تم ذبح الجرذان في نهاية الأسبوع السادس وأخذت عينات الدم لقياس مستوى الرصاص بالدم ومستوى ومؤشرات الجهد المؤکسد بالمصل (أکسيد النيتريک، الدهون فوق المؤکسدة، ومضادات الأکسدة الکلية) وکذلک وظائف الکبد والکلى بالمصل.
أوضحت نتائج الدراسة ارتفاع مستوى الرصاص بالدم ومؤشرات الجهد المؤکسد ووظائف الکبد والکلى في المجموعة التي تناولت خلات الرصاص عند إعطاء حامض الألفاليبوک أو السکسمر بمفردهما أو سوياً ظهر تحسن في المؤشرات السابقة ماعدا انخفاض مستوى الرصاص بالدم عند إعطاء حامض الألفاليبوک بمفرده، وکان التحسن أکثر وضوحاً عند إعطائهما سوياً .
ويستخلص من هذه الدراسة أن إعطاء حامض الألفاليبوک بمفرده أو مع السکسمر له تأثير مفيد في تحسن أعراض التسمم والجهد المؤکسد للرصاص، وينصح بإعطائه لعمال المصانع عند تعرضهم المهني للرصاص، وکذلک في النظام العلاجي لحالات التسمم بالرصاص مع السکسمر حيث يزيد من فاعليته.

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