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. 2024 Jan 11;25(2):941.
doi: 10.3390/ijms25020941.

Oregano (Origanum vulgare) Essential Oil and Its Constituents Prevent Rat Kidney Tissue Injury and Inflammation Induced by a High Dose of L-Arginine

Nikola M Stojanović  1 , Katarina V Mitić  2 , Milica Nešić  3 , Milica Stanković  4 , Vladimir Petrović  5 , Marko Baralić  6   7 , Pavle J Randjelović  1 , Dušan Sokolović  8 , Niko Radulović  3
Affiliations

Oregano (Origanum vulgare) Essential Oil and Its Constituents Prevent Rat Kidney Tissue Injury and Inflammation Induced by a High Dose of L-Arginine

Nikola M Stojanović et al. Int J Mol Sci. .

Abstract

This study aimed to evaluate the protective action of oregano (Origanum vulgare) essential oil and its monoterpene constituents (thymol and carvacrol) in L-arginine-induced kidney damage by studying inflammatory and tissue damage parameters. The determination of biochemical markers that reflect kidney function, i.e., serum levels of urea and creatinine, tissue levels of neutrophil-gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1), as well as a panel of oxidative-stress-related and inflammatory biomarkers, was performed. Furthermore, histopathological and immunohistochemical analyses of kidneys obtained from different experimental groups were conducted. Pre-treatment with the investigated compounds prevented an L-arginine-induced increase in serum and tissue kidney damage markers and, additionally, decreased the levels of inflammation-related parameters (TNF-α and nitric oxide concentrations and myeloperoxidase activity). Micromorphological kidney tissue changes correlate with the alterations observed in the biochemical parameters, as well as the expression of CD95 in tubule cells and CD68 in inflammatory infiltrate cells. The present results revealed that oregano essential oil, thymol, and carvacrol exert nephroprotective activity, which could be, to a great extent, associated with their anti-inflammatory, antiradical scavenging, and antiapoptotic action and, above all, due to their ability to lessen the disturbances arising from acute pancreatic damage. Further in-depth studies are needed in order to provide more detailed explanations of the observed activities.

Keywords: L-arginine; Origanum vulgare; inflammatory parameters; kidney; tissue damage parameters.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Kidney tissue NGAL (A) and KIM-1 (B) levels in rats belonging to different experimental groups. * p < 0.001 vs. vehicle-treated control (OO), ### p < 0.05; # p < 0.001 vs. AOO group; NMA—no measurable activity.
Figure 2
Figure 2
Kidney tissue MPO activity (A), NO (B), and TNF-α concentrations (C) in rats belonging to different experimental groups. *** p < 0.05; * p < 0.001 vs. vehicle-treated control (OO), # p < 0.001 vs. AOO group.
Figure 3
Figure 3
Kidney tissue caspase-3 content in rats belonging to different experimental groups. * p < 0.001 vs. vehicle-treated group (OO), # p < 0.001 vs. control; NMA—no measurable activity.
Figure 4
Figure 4
Histopathological analysis of rat kidney tissue stained with H&E (A–K, magnification ×200, except for D,E, where magnification is ×100) and PAS (L–V, magnification ×100). Rats belonging to the vehicle-, O. vulgare-, thymol-, carvacrol-, thymol, and carvacrol-treated groups (A–E,L–P, respectively) showed mainly regular kidney tissue structures with occasional inflammatory cell or tubular deposits. (F,Q) Kidneys of animals treated with L-arginine showed vascular congestion, tubular degeneration, inflammatory infiltration, occasional cell necrosis, and tubular deposits; (G,R) L-arginine and essential oil-treated animals showed minimal changes in the kidneys in the form of degeneration and occasional tubular deposit; (H,S) L-arginine and carvacrol-treated animals exerted pronounced changes in the form of tubular degeneration, inflammatory infiltrate, and blood stasis; (I,T) in L-arginine and thymol-treated animals, there was significant tubular damage and blood stasis; (J,U) the most prominent feature in L-arginine and carvacrol + thymol-treated animals was blood stasis and glomerular space narrowing; (K,V) in L-arginine and allopurinol-treated rats, only minimal changes in tubular cells and occasional glomerular space narrowing was noted.
Figure 5
Figure 5
Histopathological analysis of rat kidney tissue stained with CD95 (A–K, magnification ×100) and CD68 (L–V, magnification ×100). Rats belonging to the vehicle-, O. vulgare-, thymol-, carvacrol-, thymol-, and carvacrol-treated groups (A–E,L–P, respectively) showed mainly regular kidney tissue structures with occasional weak immunopositivity in either kidney tubule cells (CD95) or resident inflammatory cells (CD68). (F,Q) Kidneys of animals treated with L-arginine showed significant CD95 expression in tubular cells and CD68 in inflammatory cells; (G,R) L-arginine and essential oil-treated animals showed moderate CD95 expression and rare CD68; (H,S) L-arginine and carvacrol-treated animals exerted mild tubular CD95 and extensive inflammation characterized by an increase in CD68 expression; (I,T) in L-arginine and thymol-treated animals, there was a significant tubular CD95 and mild inflammatory cell CD68 expression; (J,U) in L-arginine and carvacrol + thymol-treated animals, CD95 expression was mild, as was the expression of CD68; (K,V) in L-arginine and allopurinol-treated rats, only occasional CD95 expression was found, and almost no CD68-positive cells were visible. Arrows denote CD68-positive cells.
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