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. 2021 Apr 24;38(2):159-174.
doi: 10.1007/s43188-021-00092-3. eCollection 2022 Apr.

Non-toxic nature of chebulinic acid on biochemical, hematological and histopathological analysis in normal Sprague Dawley rats

Khurram Aamir  1   2 , Vaisnevee Sugumar  3 , Hidayat Ullah Khan  1 , Chung Yeng Looi  4 , Rajesh Juneja  5 , Muhammad Waqas  2 , Aditya Arya  3   6   7   8
Affiliations

Non-toxic nature of chebulinic acid on biochemical, hematological and histopathological analysis in normal Sprague Dawley rats

Khurram Aamir et al. Toxicol Res. .

Abstract

Chebulinic acid (CA) is an ellagitannins isolated from the dried fruits of Terminalia chebula with diverse pharmacological activities. The present study focused on the acute toxicity of CA in normal Sprague Dawley (SD) rats. CA was administered via oral gavage to different groups in 300 and 2000 mg/kg body weight and vehicle respectively. All the animals were monitored carefully for any physiological or behavioral changes for 14 days. On day 15th animals were euthanized and blood was collected for hematological and biochemical analysis. Different tissues were collected for histopathological study using four different staining techniques (hematoxylin and eosin, Masson's trichrome, periodic acid Schiff and picro sirius red) to observe any pathological alterations. The results highlighted no morbidity and mortality after oral ingestion of CA (300 and 2000 mg/kg). Food and water consumption, body weight, relative organ weight, hematological and biochemical parameters were normal without any gross pathological lesions in harvested tissues. The outcome of the current study supported safety of CA even at high dose. However, further detailed study is required on experimentally disease model to unfold its therapeutic potential in laboratory animals.

Keywords: Acute oral toxicity; Biochemical analysis; Chebulinic acid; Hematological; Histopathology.

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Conflict of interest statement

Conflict of interestThe authors have no conflict of interest to disclose.

Figures

Fig. 1
Fig. 1
Acute oral toxicity test of chebulinic acid as per OECD guidelines 423. Chebulinic acid is categorized under category 5 given no toxic signs and mortality upto 2000 mg/kg body weight. MR mortality ratio, BW body weight
Fig. 2
Fig. 2
Macroscopic images of harvested organs. Macroscopic photographs displayed normal architecture of heart (a–c), liver (d–f) and brain (g–i) of the treated groups when compared with control SD rats
Fig. 3
Fig. 3
Macroscopic images of harvested organs. Macroscopic photographs displayed normal architecture of lungs (j–l), kidney (m–o), pancreas (p–r) and spleen (s–u) of the treated groups when compared with control SD rats
Fig. 4
Fig. 4
Microscopic images of harvested organs representing H&E stained cardiac, liver and brain tissues. Photomicrographs of cardiac muscles representing normal architecture with centrally placed nucleus and regular arrangement of muscle fibers (a–c), hepatic tissues also appeared normal with proper cellular outlines, well-organized, observable radiating cords and sinusoids (d–f) and brain tissues showing normal histoarchitecture exhibited normal shape of pyramidal neurons (g–i) from control and treated groups (H&E stain, × 200)
Fig. 5
Fig. 5
Microscopic images of harvested organs representing H&E stained lungs, kidney, pancreas and spleen tissues. Photomicrographs of lungs representing normal architecture presenting regular honeycomb like appearance of alveoli with proper arrangement of flattened squamous cells (j–l), renal tissues showing normal glomerular, proximal and distal tubule architecture with regular distribution of nephrons (m–o), pancreas representing uniform distribution of acinar cells with regular structural outline and visible appearance of islets of Langerhans arranged in the bunch of small groups with slightly stained cytoplasm (p–r) and spleen demonstrating regular morphological features with visible white pulp composed of compact and diffused distribution of lymphocytes and red pulp revealing visible sinusoids (s–u) from control and treated groups (H&E stain, × 200). PCT Proximal convoluted tubules), DCT distal convoluted tubules
Fig. 6
Fig. 6
Microscopic images of harvested organs displaying massion trichrome stained cardiac, liver and brain tissues. Photomicrographs of cardiac tissue displaying normal architecture without hypertrophic, fibrotic and necrotic signature (a–c), liver tissues representing no evident apoptotic and necrotic lesions (d–f) and brain showing regular morphology without necrosis and neuronal damage (g–i) of control and treated groups (Massion trichrome stain, × 200)
Fig. 7
Fig. 7
Microscopic images of harvested organs displaying massion trichrome stained lungs, kidney, pancreas and spleen tissues. Photomicrographs of lungs demonstrating normal architecture of lungs without observable signs of necrosis and apoptosis in bronchioles (j–l), kidney tissues showing no nephrotic vascular damage and necrotic lesions (m–o), pancreas representing no evidence of fibrosis and necrosis of islets of Langerhans (p–r) and spleen also displayed normal histoarchitecture without apoptosis and necrosis (s–u) from control and treated groups (Massion trichrome stain, × 200). PCT Proximal convoluted tubules, DCT distal convoluted tubules
Fig. 8
Fig. 8
Microscopic images of harvested organs showing periodic acid Schiff stained cardiac, liver and brain tissues. Photomicrographs of heart (a–c), liver (d–f) and brain (g–i) demonstrating no accumulation of glycogen and mucopolysaccharides from control and treated groups (periodic acid Schiff stain, × 200)
Fig. 9
Fig. 9
Microscopic images of harvested organs showing Periodic acid Schiff stained lungs, kidney, pancreas and spleen tissues. Photomicrographs of lungs (j–l), kidney (m–o), pancreas (p–r) and spleen (s–u) showing no accumulation of glycogen and mucopolysaccharides from control and treated groups (Periodic acid Schiff stain, × 200). PCT Proximal convoluted tubules, DCT distal convoluted tubules
Fig. 10
Fig. 10
Microscopic images of harvested organs demonstrating Picro sirius red stained cardiac, liver and brain tissues. Photomicrographs of heart (a–c), liver (d–f) and brain (g–i) displaying no deposition of collagen I and III fibers from control and treated groups (Picro sirius red stain, × 200)
Fig. 11
Fig. 11
Microscopic images of harvested organs demonstrating Picro sirius red stained lungs, kidney, pancreas and spleen tissues. Photomicrographs of lungs (j–l), kidney (m–o), pancreas (p–r) and spleen (s–u) demonstrating no evidence of collagen I and III deposition from control and treated groups (Picro sirius red stain, × 200). PCT Proximal convoluted tubules, DCT distal convoluted tubules
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References

    1. Ekor M. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol. 2014;4:1–10. doi: 10.3389/fphar.2013.00177. - DOI - PMC - PubMed
    1. Petrovska BB. Historical review of medicinal plants’ usage. Pharmacogn Rev. 2012;6:1–5. doi: 10.4103/0973-7847.95849. - DOI - PMC - PubMed
    1. Yuan H, Ma Q, Ye L, Piao G. The traditional medicine and modern medicine from natural products. Molecules. 2016;21:1–18. doi: 10.3390/molecules21050559. - DOI - PMC - PubMed
    1. Khan H. Medicinal plants in light of history: recognized therapeutic modality. Evid Based Complement Altern Med. 2014;19:216–219. doi: 10.1177/2156587214533346. - DOI - PubMed
    1. Dias DA, Urban S, Roessner U. A historical overview of natural products in drug discovery. Metabolites. 2012;2(2):303–336. doi: 10.3390/metabo2020303. - DOI - PMC - PubMed

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