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Abstract <p><b>Objective:</b> The use of high doses of ivermectin (IVM) has been supported by several studies for the treatment of human diseases such as COVID-19, as well as for veterinary applications, including its inclusion in fish farm feed. However, these high doses pose a risk of toxicity, highlighting the need to identify protective agents-such as folic acid (FA) and vitamin B12 (Vit.B12) that can mitigate these effects. Therefore, the current study aimed to investigate the impact of chronic exposure to IVM on blood parameters and the histoarchitectonics of the liver and kidneys in adult albino rats, as well as to assess the potential protective roles of FA and Vit.B12 against IVM-induced toxicity. <b>Material and methods:</b> Twenty-eight male albino rats were randomly divided into four groups, with seven rats in each group. The first group served as the control (Ctrl group) and received distilled water. The second group (IVM group) was subcutaneously injected with IVM. The third group (IVM + FA group) received subcutaneous injections of IVM and oral administration of FA. The fourth group (IVM + vitamin B12) received subcutaneous IVM injections along with intramuscular injections of vitamin B12. After 30 days, blood samples were collected for hematological analysis. Additionally, liver and kidney tissues were harvested for histopathological examination. <b>Results and discussion:</b> Results showed that the IVM group exhibited a slight decrease in hemoglobin (HB), red blood cells (RBCs), hematocrit, and mean corpuscular volume (MCV), as well as a significant decrease in mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). There was also a significant decrease in leukocytes and lymphocytes, accompanied by a significant increase in neutrophils, monocytes, and platelets. <b>Conclusions:</b> Histopathological analysis of the liver and kidneys revealed that IVM caused severe structural damage, including dilated blood vessels, inflammatory cell infiltration, hepatocyte ballooning, and necrosis in liver tissue. Renal tissue showed various pathological changes such as segmented or destroyed glomeruli and dilated Bowman’s space. Treatment with FA and Vit.B12 restored hematological and immunological parameters to near-normal levels and improved liver and kidney structures toward normal histology. In conclusion, FA and vitamin B12 demonstrated a protective effect against IVM-induced toxicity in rats.</p>

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Impact of Chronic Ivermectin Toxicity on Some Blood Parameters and Liver and Kidney Histoarchitectonics of Adult Albino Rats: Evaluation of the Role of Folic Acid and Vitamin B12 as New Treatment Modalities

  • 期刊论文

  • 发表日期：

    2025年7月28日

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  • Asmaa M. Mosa,
  • Rana A. Ali,
  • Seham A. Mobarak,
  • Zeinab A. Mar’ie,
  • Yahia A. Amin

摘要

Abstract

Objective: The use of high doses of ivermectin (IVM) has been supported by several studies for the treatment of human diseases such as COVID-19, as well as for veterinary applications, including its inclusion in fish farm feed. However, these high doses pose a risk of toxicity, highlighting the need to identify protective agents-such as folic acid (FA) and vitamin B12 (Vit.B12) that can mitigate these effects. Therefore, the current study aimed to investigate the impact of chronic exposure to IVM on blood parameters and the histoarchitectonics of the liver and kidneys in adult albino rats, as well as to assess the potential protective roles of FA and Vit.B12 against IVM-induced toxicity. Material and methods: Twenty-eight male albino rats were randomly divided into four groups, with seven rats in each group. The first group served as the control (Ctrl group) and received distilled water. The second group (IVM group) was subcutaneously injected with IVM. The third group (IVM + FA group) received subcutaneous injections of IVM and oral administration of FA. The fourth group (IVM + vitamin B12) received subcutaneous IVM injections along with intramuscular injections of vitamin B12. After 30 days, blood samples were collected for hematological analysis. Additionally, liver and kidney tissues were harvested for histopathological examination. Results and discussion: Results showed that the IVM group exhibited a slight decrease in hemoglobin (HB), red blood cells (RBCs), hematocrit, and mean corpuscular volume (MCV), as well as a significant decrease in mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). There was also a significant decrease in leukocytes and lymphocytes, accompanied by a significant increase in neutrophils, monocytes, and platelets. Conclusions: Histopathological analysis of the liver and kidneys revealed that IVM caused severe structural damage, including dilated blood vessels, inflammatory cell infiltration, hepatocyte ballooning, and necrosis in liver tissue. Renal tissue showed various pathological changes such as segmented or destroyed glomeruli and dilated Bowman’s space. Treatment with FA and Vit.B12 restored hematological and immunological parameters to near-normal levels and improved liver and kidney structures toward normal histology. In conclusion, FA and vitamin B12 demonstrated a protective effect against IVM-induced toxicity in rats.