Long-term treatment with chaethomellic acid A reduces glomerulosclerosis and arteriolosclerosis in a rat model of chronic kidney disease

Abstract

The high prevalence of end-stage renal disease emphasizes the failure to provide therapies to effectively prevent and/or reverse renal fibrosis. Therefore, the aim of this study was to evaluate the effect of long-term treatment with chaethomellic acid A (CAA), which selectively blocks Ha-Ras farnesylation, on renal mass reduction-induced renal fibrosis. Male Wistar rats were sham-operated (SO) or subjected to 5/6 renal mass reduction (RMR). One week after surgery, rats were placed in four experimental groups: SO: SO rats without treatment (n=13); SO+CAA: SO rats treated with CAA (n=13); RMR: RMR rats without treatment (n=14); and RMR+CAA: RMR rats treated with 2 CAA (n=13). CAA was intraperitoneally administered in a dose of 0.23 µg/Kg three times a week for six months. Renal fibrosis was evaluated by two-dimensional ultrasonography and histopathological analysis. The kidneys of the RMR animals treated with CAA showed a significantly decrease in the medullary echogenicity (p<0.05) compared with the RMR rats that received no treatment. Glomerulosclerosis and arteriolosclerosis scores were significantly lower (p<0.001) in the RMR+CAA group when compared with the RMR group. There were no significant differences in interstitial fibrosis, interstitial inflammation and tubular dilatation scores between the RMR+CAA and RMR groups. These data suggest that CAA can be a potential future drug to attenuate the progression of chronic kidney disease.

Sugar-Lowering Drugs for Type 2 Diabetes Mellitus and Metabolic Syndrome—Strategies for In Vivo Administration: Part-II

“…The administration routes that require less manipulation techniques are recommended [68]. In animal experimentation, several routes for substance administration are currently available, namely enteral (through the digestive tract), either oral (into the mouth) or gavage (esophageal, gastric, nasogastric or orogastric), intravenous (into a blood vessel), epicutaneous (onto the skin), intradermal (into the skin), subcutaneous (under the skin), transdermal (across the skin), intramuscular (into a muscle), transcorneal (onto the eye), intraocular (into the eye), intracerebral (into the brain), epidural (into the dura mater surrounding space), intrathecal (into distal spinal cord surrounding space), intraperitoneal (into the peritoneal cavity), intraosseous (into the marrow cavity), intranasal (sprayed into the nose and then absorbed by the nasal mucous membranes or into the lungs), intratracheal (into the lungs by direct tracheal instillation), inhalation, and other less common techniques, such as those using other body natural orifices, surgical exposure, and others regarding species-specific anatomic features [68,69,70,71,72].…”

Stevioside inhibits unilateral ureteral obstruction‐induced kidney fibrosis and upregulates renal PPARγ expression in mice

“…The former was to examine the general changes of pathomorphology, which was expressed as histopathological scores according to the description of Nogueira et al. (2017). The latter was to evaluate the degree of collagen deposition, which was expressed as collagen area’s ratio according to our description (Wang et al, 2019).…”

“…To observe the histological changes of kidney, the partial renal tissues were fixed in 4% of formaldehyde solution and embedded in paraffin for hematoxylin and eosin (HE) staining and Van Gieson (VG) staining. The former was to examine the general changes of pathomorphology, which was expressed as histopathological scores according to the description of Nogueira et al (2017). The latter was to evaluate the degree of collagen deposition, which was expressed as collagen area's ratio according to our description (Wang et al, 2019).…”

Dissecting the Involvement of Ras GTPases in Kidney Fibrosis

“…In the experimental model of 5/6 renal mass reduction [RMR] in rats, long-term administration of chaetomellic acid decreased the oxidative stress in kidneys [ 126 ]. Using the same RMR model, the same authors found a decrease in glomerulosclerosis and arteriolosclerosis after chaetomellic acid administration [ 127 ].…”