Chemical Profile of Cyperus laevigatus and Its Protective Effects against Thioacetamide-Induced Hepatorenal Toxicity in Rats

Abstract

Cyperus species represent a group of cosmopolitan plants used in folk medicine to treat several diseases. In the current study, the phytochemical profile of Cyperus laevigatus ethanolic extract (CLEE) was assessed using UPLC-QTOF-MS/MS. The protective effect of CLEE at 50 and 100 mg /kg body weight (b.w.) was evaluated on hepatorenal injuries induced by thioacetamide (100 mg/kg) via investigation of the extract's effects on oxidative stress, inflammatory markers and histopathological changes in the liver and kidney. UPLC-QTOF-MS/MS analysis of CLEE resulted in the identification of 94 compounds, including organic and phenolic acids, flavones, aurones, and fatty acids. CLEE improved the antioxidant status in the liver and kidney, as manifested by enhancement of reduced glutathione (GSH) and coenzyme Q10 (CoQ10), in addition to the reduction in malondialdehyde (MDA), nitric oxide (NO), and 8-hydroxy-2'-deoxyguanosine (8OHdG). Moreover, CLEE positively affected oxidative stress parameters in plasma and thwarted the depletion of hepatorenal ATP content by thioacetamide (TAA). Furthermore, treatment of rats with CLEE alleviated the significant increase in plasma liver enzymes, kidney function parameters, and inflammatory markers. The protective effect of CLEE was confirmed by a histopathological study of the liver and kidney. Our results proposed that CLEE may reduce TAA-hepatorenal toxicity via its antioxidant and anti-inflammatory properties suppressing oxidative stress.

Keywords: aurones; flavonoids; hepatorenal injuries; histopathology; inflammation markers; oxidative stress; smooth flatsedge.

Figure 1

UPLC-QTOF–MS base peak chromatogram of CLEE in negative ion mode. Peaks are numbered following that listed in Table 1.

Figure 2

Representative structures of major metabolites identified in CLEE and peak names follow the numbers stated in Table 1.

Figure 3

Effect of CLEE on liver function parameters of rats intoxicated by TAA. Each value represents the mean of six animals ± SE. Statistical analysis was performed using one-way ANOVA followed by the Tukey-Kramer multiple comparisons test. (* vs. control group, @ vs. TAA group and ^# vs. TAA + 50 mg /kg b.w. CLEE group) at p < 0.05.

Figure 4

Effect of CLEE on kidney function parameters of rats intoxicated by TAA. Each value represents the mean of six animals ± SE. Statistical analysis was performed using one-way ANOVA followed by the Tukey-Kramer multiple comparisons test. (* vs. control group, @ vs. TAA group) at p < 0.05.

Figure 5

Effect of C. laevigatus EtOH extract (CLEE) on plasma oxidative stress and inflammatory parameters of rats intoxicated by TAA. Each value represents the mean of six animals ± SE. Statistical analysis was performed using one-way ANOVA followed by the Tukey-Kramer multiple comparisons test. (* vs. control group, @ vs. TAA group and # vs. TAA + 50 mg /kg b.w. CLEE group) at p < 0.05.

Figure 6

Effect of C. laevigatus EtOH extract (CLEE) on hepatic oxidative stress and energy parameters of rats intoxicated by TAA. Each value represents the mean of six animals ± SE. Statistical analysis was performed using one-way ANOVA followed by the Tukey-Kramer multiple comparisons test. (* vs. control group, and @ vs. TAA group) at p < 0.05.

Figure 7

Effect of C. laevigatus EtOH extract (CLEE) on renal oxidative stress and energy parameters of rats intoxicated by TAA. Each value represents the mean of six animals ± SE. Statistical analysis was performed using one-way ANOVA followed by the Tukey-Kramer multiple comparisons test. (* vs. control group, and @ vs. TAA group) at p < 0.05.

Figure 8

A photomicrograph of (A) rat liver of control group showing normal hepatic architecture. Central vein (CV), blood sinusoids (S) and nucleus (N) are found; (B) rat liver intoxicated by TAA showing disorganized hepatocytes, fibrosis with inflammatory cell proliferation in between the congested portal vein, aggregation of inflammatory cells (arrow), bridging of fibroblast-like cells, degeneration changes with cytoplasmic necrotic areas, and deeply pyknotic nuclei, (H & E stain, Scale bar: 60 µm); (C) liver from rats administered TAA and 50 mg/kg b.w. of CLEE showing mild to moderate fibrosis with thin bridging fibroblasts, inflammatory cell infiltration around central vein (arrow), degeneration, mild necrosis (arrowhead), dilated sinusoids (S), and pyknotic nuclei (P); and (D): liver from rats administered TAA with 100 mg /kg b.w. of CLEE showing few degenerative hepatocytes with less fibrosis and thin bridging fibroblasts, dilated sinusoids (S), and pyknotic nuclei; (E) kidney section of control group showing normal structure of the glomerulus (G), urinary space (US), Proximal convoluted tubule (PCT) and distal convoluted tubule (DCT); (F) kidney section of rats intoxicated by TAA, showing shrunken glomeruli (G) with dilated capsular spaces (US), tubular epithelial cell degeneration, and necrosis associated with pyknotic nuclei (P); (G) kidney section of rats administered TAA and 50 mg/kg b.w. of CLEE showing moderated degeneration (arrow head), pyknotic nuclei (P) observed in tubules epithelial cells; (H) kidney section of rats administered TAA and 100 mg/kg b.w. of CLEE showing improved degeneration of tubules (arrow head) and pyknotic nuclei (P). (H & E stain, Scale bar: 30 µm).