Hepatotoxicity of Methotrexate and Possible Ameliorative Effect of L-Carnitine: Histological and Ultrastructural Study
Najwa AbdalgaderAhmad Algaw;
Abstract
Methotrexate (MTX), a folic acid antagonist, is a chemotherapeutic agent widely used in the treatment of some types of cancers and various inflammatory diseases such as psoriasis and rheumatoid arthritis.
The efficacy of this agent in high doses has been associated with hepatotoxicity. L-Carnitine (LC) is a small water-soluble molecule which plays an important role in fat metabolism. It is essential for the normal mitochondrial oxidation of fatty acids and excretion of acyl-coenzyme A (acyl-CoA) esters and affects adenosine triphosphate levels.
The present study aimed to investigate the protective effect of L-Carnitine against Methotrexate induced hepatotoxicity on the rat liver . Fifty male albino rats weighing 120-130g.were used to study the histological and ultrastructural alterations as well as histochemical changes-including total proteins and total polysaccharides in liver tissues.The experimental animals were equally divided into five groups , 10 rats each, and treated as follows : (1) rats did not receive any treatment (control group ); (2) rats given 300mg L-Carnitine /100g b.w. for 4 weeks ; (3) rats given 0.045mg Methotrexate /100g b.w. for 4 weeks ; (4) rats given 0.045mg Methotrexate /100g b.w. with 300mg L-Carnitine /100g b.w. for 4 weeks ; (5) rats given 0.045mg Methotrexate /100g b.w. for 4 weeks then given 300mg L-Carnitine /100g b.w. for another 4 weeks . Rats were injected intraperitoneally twice per week.
The results of the present study in methotrexate group showed dilatation and congestion of blood vessels with collection of chronic inflammatory cells, severe ballooning and vacuolation of hepatocytes.Some nuclei of the degenerated cells showed pyknosis while other showed karyolysis .Enlarged von kupffer cells within dilated sinusoids were also detected,in addition to haemorrhagic and vacuolar necrosis .Histochemical studies showed that methotrexate decreased total proteins and polysaccharides in the liver tissues. Ultrastructure studies revealed Dilatation and congestion of the hepatic sinusoids. pyknotic nucleus with abnormally electron dense chromatin as well as irregular nuclear membrane ,electron dense mitochondria , fragmented rough endoplasmic reticulum , increased lipid droplets and increased collagen fibers.
Methotrexate + L-Carnitine group, showed significant improvement in the histological, histochemical and ultrastructural alterations.
In Methotrexate then L-Carnitine group, showed mild to moderate improvement in all these changes caused by methotrexate. These results indicated that co- and post administration of L-Carnitine reduced the histological,histochemical and ultrastructural changes and induce mild protection against methotrexate toxicity.
The efficacy of this agent in high doses has been associated with hepatotoxicity. L-Carnitine (LC) is a small water-soluble molecule which plays an important role in fat metabolism. It is essential for the normal mitochondrial oxidation of fatty acids and excretion of acyl-coenzyme A (acyl-CoA) esters and affects adenosine triphosphate levels.
The present study aimed to investigate the protective effect of L-Carnitine against Methotrexate induced hepatotoxicity on the rat liver . Fifty male albino rats weighing 120-130g.were used to study the histological and ultrastructural alterations as well as histochemical changes-including total proteins and total polysaccharides in liver tissues.The experimental animals were equally divided into five groups , 10 rats each, and treated as follows : (1) rats did not receive any treatment (control group ); (2) rats given 300mg L-Carnitine /100g b.w. for 4 weeks ; (3) rats given 0.045mg Methotrexate /100g b.w. for 4 weeks ; (4) rats given 0.045mg Methotrexate /100g b.w. with 300mg L-Carnitine /100g b.w. for 4 weeks ; (5) rats given 0.045mg Methotrexate /100g b.w. for 4 weeks then given 300mg L-Carnitine /100g b.w. for another 4 weeks . Rats were injected intraperitoneally twice per week.
The results of the present study in methotrexate group showed dilatation and congestion of blood vessels with collection of chronic inflammatory cells, severe ballooning and vacuolation of hepatocytes.Some nuclei of the degenerated cells showed pyknosis while other showed karyolysis .Enlarged von kupffer cells within dilated sinusoids were also detected,in addition to haemorrhagic and vacuolar necrosis .Histochemical studies showed that methotrexate decreased total proteins and polysaccharides in the liver tissues. Ultrastructure studies revealed Dilatation and congestion of the hepatic sinusoids. pyknotic nucleus with abnormally electron dense chromatin as well as irregular nuclear membrane ,electron dense mitochondria , fragmented rough endoplasmic reticulum , increased lipid droplets and increased collagen fibers.
Methotrexate + L-Carnitine group, showed significant improvement in the histological, histochemical and ultrastructural alterations.
In Methotrexate then L-Carnitine group, showed mild to moderate improvement in all these changes caused by methotrexate. These results indicated that co- and post administration of L-Carnitine reduced the histological,histochemical and ultrastructural changes and induce mild protection against methotrexate toxicity.
Other data
| Title | Hepatotoxicity of Methotrexate and Possible Ameliorative Effect of L-Carnitine: Histological and Ultrastructural Study | Other Titles | السمية الكبدية لعقار الميثوتريكسات و الوقاية المحتملة لمادة ل- كارنيتين: دراسة نسيجية و تركيبية دقيقة | Authors | Najwa AbdalgaderAhmad Algaw | Issue Date | 2017 |
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