Anat Cell Biol.  2024 Sep;57(3):446-458. 10.5115/acb.24.054.

Edible mushroom (Pleurotus cornucopiae) extract vs. glibenclamide on alloxan induced diabetes: sub-acute in vivo study of Nrf2 expression and renal toxicity

• Uzomba CG
• Ezemagu UK
• Ofoegbu MS
• Lydia N
• Goodness E
• Emelike C
• Obinna U
• Nwafor AJ
• Mbajiorgu EF

• KMID: 2559764
• DOI: http://doi.org/10.5115/acb.24.054

Abstract

The study aims to compare the action of Pleurotus cornucopiae and glibenclamide on alloxan-induced diabetes and ascertain how an aqueous extract of the edible mushroom regulates the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), oxidative stress biomarkers and renal toxicity in a diabetic male Wistar rat model. Twenty-five adult male Wistar rats were randomly grouped into five groups with five rats per. Group 1 and those in the treatment groups received normal feed and water ad libitum. Group 2 received intraperitoneal administration of alloxan monohydrate (150 mg/kg body weight). Group 3 received alloxan monohydrate and glibenclamide (5 mg/kg body weight bwt), group 4 received alloxan monohydrate plus the extract (250 mg/kg bwt) and group 5 received alloxan monohydrate plus the extract (500 mg/kg bwt). The administration of glibenclamide plus the extract was oral for 14 days. Glibenclamide and the extract lowered blood glucose level, catalase, and glutathione peroxidase activities, increased the superoxide dismutase (SOD) activity in rats with alloxan induced diabetes. The extract at 500 mg/kg bwt reduced the plasma urea and sodium concentration in the treated rats. The extract and glibenclamide could detoxify alloxan and restore its induced renal degeneration and glomeruli atrophy, intra renal hemorrhage and inflammation and oxidative biomarkers through activation of Nrf2 expression. The drug glibenclamide and P. cornucopiae have appreciable hypoglycemic activity and potential to restore the normal renal architecture in the rats, hence they offer similar curative effects. Additionally, the extract at 500 mg/kg bwt activated SOD and Nrf2 expression more than glibenclamide in rats with alloxan-induced diabetes.

Keyword

Mushroom; Diabetes mellitus; Nrf2; Glibenclamide; Renal failure

Figure

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  Fig. 1 Pathways of toxicity alloxan and streptozotocin in beta cells, leading to diabetes induction. Adapted from Lenzen. Diabetologia 2008;51:216-26, with permission [33].

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  Fig. 2 Fruiting bodies of Pleurotus cornucopiae grown at animal house, AE-FUNAI.

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  Fig. 3 Photomicrograph of the rat kidney treated with the kidney sections are shown in 10× magnification stained with haematoxylin and eosin. Group (A) control with normal kidney histology with glomerulus (G), intact Bowman’s capsule, proximal convoluted tubules (PCT), distal convoluted tubules (DCT). No capillary congestion, haemorrhage, and interstitial damage. (B) Diabetic group with necrotic glomeruli (NG), generally distorted renal tubular arrangement, undefined proximal, distal convoluted tubules, interstitial damage, capillary congestion, and hemorrhages (H). (C) Standard drug group with white arrowheads showing urinary space shrinkage, NG, normal proximal and distal convoluted tubules (PCT, DCT). (D) Low dose group with several NG, distorted proximal and distal convoluted tubules, interstitial damage (asterisk), inflammations (red bold arrows), atrophied glomerulus (AG). (E) High dose group regenerating glomeruli (black arrows) with Bowman’s capsules, tubular regeneration with well-defined proximal, distal convoluted tubules and resolving interstitial damage, capillary congestion, and hemorrhages, showing protection in this group. BS, Bowman’s space.

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  Fig. 4 Immunohistochemistry photomicrographs (500× magnification) of Nfr2 expression in kidney tissue of male wistar rats in diabetes, and treated with glibenclamide and mushroom (Pleurotus cornucopiae) magnification ×400. (A) Control (group 1), (B) diabetic control (group 2), (C) diabetic rats+Glibenclamide (group 3), (D) diabetic rats+250 mg/kg P. cornucopiae (group 4), (E) diabetic rats+500 mg/kg P. cornucopiae (group 5). Red arrow shows the expression of Nrf2. Appearance of brown yellow staining in cytoplasm of renal tubular cells in group 1. Positive nuclear staining was observed in groups 3, 4, and 5 indicating regeneration of glomeruli (red arrows) with Bowman’s capsules, tubular regeneration with well-defined proximal, distal convoluted tubules and resolving interstitial damage, capillary congestion and hemorrhages, showing protection in this group. An indication regeneration of glomeruli (red arrows) with Bowman’s capsules, tubular regeneration with well-defined proximal, distal convoluted tubules and resolving interstitial damage, capillary congestion and hemorrhages, showing protection in this group. aStatistically (P<0.05) significant mean difference with normal control.

Reference

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