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. 2022 Jan;35(1):45-52.
doi: 10.1293/tox.2021-0003. Epub 2021 Oct 9.

Evaluation of Caspase-3 and Ki-67 expression in squamous cell hyperplasia of the stomach induced by Platycodi radix water extract in Sprague-Dawley rats

Yinghua Li  1 , Seung-Beom Cha  2 , Youngil Park  3   4 , Bo-Ho Gong  2 , In-Yeong Jeong  2 , Hak-Soo Kim  2 , Min-Soo Kang  2 , Young-Suk Kim  2 , Chang Hoon Han  2 , Hyun-Kul Lee  2 , Si-Whan Song  2 , Chae-Gyoo Park  3 , Boo-Hyon Kang  2
Affiliations

Evaluation of Caspase-3 and Ki-67 expression in squamous cell hyperplasia of the stomach induced by Platycodi radix water extract in Sprague-Dawley rats

Yinghua Li et al. J Toxicol Pathol. 2022 Jan.

Abstract

Platycodi radix is widely used in traditional herbal medicine for the treatment of bronchitis, asthma, pulmonary tuberculosis, hypertension, hyperlipidemia, and diabetes. This study aimed to investigate cell proliferation (Ki-67) and apoptosis (Caspase-3) potential in squamous cell hyperplasia of the stomach induced by a Platycodi radix water extract in a subchronic toxicity study. One hundred formalin-fixed, paraffin-embedded stomach tissues of rats treated with Platycodi radix at doses of 0, 500, 1,000, and 3,000 mg/kg body weight/day were used for the analysis. They were conventionally stained using hematoxylin and eosin (H&E) and immunohistochemically (IHC) stained using caspase-3 and Ki-67 antibodies. The incidence of squamous cell hyperplasia was significantly increased in the 3,000 mg/kg b.w./day treatment group in both sexes (p<0.01). However, the hyperplastic change was completely repaired after 4 weeks of recovery period. Ki-67 expression was similar in all groups, with no statistically significant differences among the groups. Caspase-3 expression was significantly increased in both sexes in the 3,000 mg/kg b.w./day treatment group (p<0.01), compared with the vehicle control groups, and then reduced to normal levels in the recovery groups in both sexes. In conclusion, this study showed that squamous cell hyperplasia induced by the Platycodi radix water extract in the limiting ridge of the stomach is not considered to be abnormal proliferative change; as a result, squamous cell hyperplasia is considered to be a non-adverse effect when induced by the oral administration of the Platycodi radix water extract once daily for 13 weeks in rats.

Keywords: Caspase-3; Ki-67 antigen; Sprague–Dawley rats; local irritation; squamous cell hyperplasia.

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Figures

Fig. 1.
Fig. 1.
The normal epithelium of stomach was observed in a male of control group (A and C). The stomach was divided into the non-glandular (right) and glandular stomach (left). The limiting ridge had solitary papillary fold at the junction between non-glandular and glandular stomach. Squamous cell hyperplasia of limiting ridge (left) was observed in the stomach in a male of 3,000 mg/kg b.w./day treatment group (B and D). The squamous cell hyperplasia was evident in the limiting ridge of stomach and was characterized by thickening of the stratified squamous epithelium and hyperkeratosis. Caspase-3 expression were mainly located in the spinous layers of squamous epithelium in the limiting ridge of stomach (C and D). Caspase-3 was highly expressed in the epithelium with squamous cell hyperplasia (D) than the normal epithelium (C). A and B: H&E staining, C and D: Caspase-3 staining.
Fig. 2.
Fig. 2.
In the main group of both sexes, C aspase-3 expression was significantly increased in 3,000 mg/kg b.w./day (M-G4) group than in control or any other treated group (M-G1, M-G2, M-G3, **: p<0.01). No significant change in the recovery group was observed in 3,000 mg/kg b.w./day (R-G4) compared to recovery control group (R-G1) of both sexes. M: main; G: group; R: recovery.
Fig. 3.
Fig. 3.
Caspase-3 expression was significantly increased in the squamous cell hyperplasia (**: p<0.01) than in the normal epithelium in the stomach in both sexes.
See this image and copyright information in PMC

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