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. 2011:2011:717921.
doi: 10.1155/2011/717921. Epub 2010 Sep 7.

KIOM-79 Prevents Lens Epithelial Cell Apoptosis and Lens Opacification in Zucker Diabetic Fatty Rats

Junghyun Kim  1 , Chan-Sik Kim, Eunjin Sohn, Hyojun Kim, Il-Ha Jeong, Jin Sook Kim
Affiliations

KIOM-79 Prevents Lens Epithelial Cell Apoptosis and Lens Opacification in Zucker Diabetic Fatty Rats

Junghyun Kim et al. Evid Based Complement Alternat Med. 2011.

Abstract

Damage of lens epithelial cells (LECs) has been implicated in cataract formation. The aim of this study was to investigate the protective effect of KIOM-79, a combination of four plant extracts, on LECs. We examined the levels of advanced glycation end products (AGEs), nuclear factor-kappaB (NF-κB) activation and inducible nitric oxide synthase (iNOS) expression in LECs during cataract development using the Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes. KIOM-79 was orally administered by gavage to ZDF rats once a day for 13 weeks. Apoptosis was detected by TUNEL assay, and NF-κB activation and iNOS expression were studied by southwestern histochemistry and immunohistochemistry, respectively. In diabetic cataractous lenses, TUNEL-positive LECs were markedly increased 20-fold, and AGEs were highly accumulated (2.7-fold) in LECs. In addition, both NF-κB activation, and iNOS expression were significantly enhanced 3- to 5-fold, respectively, compared to levels found in normal ZL rats. However, the administration of KIOM-79 delayed the development of diabetic cataracts and prevented LEC apoptosis (70%) through the inhibition of AGEs, NF-κB-activation and iNOS expression. These observations suggest that KIOM-79 is useful in inhibiting diabetic cataractogenesis and acts through an antiapoptotic mechanism to protect LECs from injury.

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Figures

Figure 1
Figure 1
Analysis of lens opacity. Representative images of lenses in each group. Lens opacity was analyzed (score 0 to 4) from each lens from a normal Zucker lean rat (ZL), Zucker diabetic fatty rat (ZDF), and ZDF rat treated with KIOM-79 (KIOM-79). All data are expressed as means ± SE, n = 8. *P < .01 versus vehicle-treated ZDF rats.
Figure 2
Figure 2
Apoptosis of LECs. (a) The lens sections from a normal Zucker lean rat (ZL), vehicle-treated ZDF rat (ZDF), and ZDF rat treated with KIOM-79 (KIOM-79) were stained with a TUNEL kit. Apoptotic LECs (arrow) were observed in vehicle-treated ZDF rats. (b) Immunofluorescence staining of cleaved caspase-3. Immunofluorescence signals for cleaved caspase-3 (red) were mainly detected in the lens epithelium of ZDF rats. X400 magnification. (c and d) Quantitative analysis of TUNEL-positive and cleaved caspase-3-positive cells in LECs. All data are expressed as means ± SE, n = 8. *P < .01 versus normal ZL rats, # P < .01 versus vehicle-treated ZDF rats.
Figure 3
Figure 3
AGE accumulation. (A) Immunohistochemical localization of AGEs in lens from a normal Zucker lean rat (ZL), vehicle-treated ZDF rat (ZDF) and ZDF rat treated with KIOM-79 (KIOM-79). A strong AGE immunoreactivity was observed in the cytoplasm of LECs and lens fibers of vehicle-treated ZDF rats. In contrast, immunoreactivity in lenses of KIOM-79-treated ZDF rats was decreased. X400 magnification. (B) Quantitative analysis of AGE immunoreactive intensity. (C) Western blot analysis of AGEs. Values in the bar graphs represent means ± SE, n = 8. *P < .01 versus normal ZL rats, # P < .01 versus vehicle-treated ZDF rats.
Figure 4
Figure 4
The expression pattern of iNOS. (a) Immunohistochemical localization of iNOS protein. iNOS immunoreactivity (arrow) was observed in the cytoplasm of LECs of diabetic lenses. The immunoreactivity in KIOM-79-treated rats was decreased in its intensity. ZL: normal Zucker lean rat; ZDF: vehicle-treated ZDF rat; KIOM-79: ZDF rat treated with KIOM-79. X400 magnification. (b) Quantitative analysis of iNOS protein signal intensity. Values in the bar graphs represent means ± SE, n = 8. *P < .01 versus normal ZL rats, # P < .01 versus vehicle-treated ZDF rats.
Figure 5
Figure 5
Distribution of NF-κB in LECs detected by southwestern histochemistry. (a) Representative photomicrograph of lens from a normal Zucker lean rat (ZL), vehicle-treated ZDF rat (ZDF), and ZDF rat treated with KIOM-79 (KIOM-79). Positive signals (arrow) for activated NF-κB were mainly detected in nuclei of LECs of the vehicle-treated ZDF rat. X400 magnification. (b) Quantitative analysis of positive cells in LECs. Values in the bar graphs represent means ± SE, n = 8. *P < .01 versus normal ZL rats, # P < .01 versus vehicle-treated ZDF rats.
Figure 6
Figure 6
Proposed mechanism for the protective effect of KIOM-79 against lens epithelial cell apoptosis in Zucker diabetic fatty rats.
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