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Protective mechanisms of protocatechuic acid against doxorubicin-induced nephrotoxicity in rat model
Olorunfemi R Molehin1, Anne A Adeyanju2, Stephen A Adefegha3
1Department of Biochemistry, Faculty of Science, Ekiti State University, Ado-Ekiti P.M.B.5363, Ado-Ekiti, Nigeria, Phone: +234-803-462-1267.
Abstract:
Background Doxorubicin (DOX) induces toxicity in many tissues/organs, including the heart, kidney and so on. This study was designed to evaluate the modulatory effects of protocatechuic acid (PCA) against DOX-induced nephrotoxicity in rats. Animals were randomly grouped into five groups. Methods Group 1 served as the normal control (CTR). A single dose of DOX at 20 mg/kg was administered intraperitoneally (i.p.) to animals in Group 2. Groups 3 and 4 were pretreated with PCA for 5 days (doses of 10 and 20 mg/kg body weight, respectively) after which DOX was injected (PCA-10 + DOX and PCA-20 + DOX). Group 5 received PCA only at a dose of 20 mg/kg body weight (PCA-20). Results The results revealed significant elevations (p < 0.05) in malondialdehyde content, expressions of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX2) in the kidney. Likewise, increased serum levels of creatinine and urea of DOX group were observed. A significant decrease (p < 0.05) in glutathione (GSH) level and antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione s- transferase (GST) activities in the kidney were observed compared with the control. Pretreatment with PCA (10 and 20 mg/kg, p.o.) for 5 days prior to the i.p. injection of DOX reduced MDA levels, modulated iNOS and COX2 activities and improved kidney function markers as well as oxidative stress parameters. Findings from the histopathology studies confirms the protective effects of PCA on DOX-induced damage on the kidney cells. Conclusions This study has demonstrated the anti-inflammatory and antioxidative properties of PCA, which could be part of its possible protective mechanisms against nephrotoxicity induced by DOX.
Insights
Protocatechuic acid (PCA) protects against Doxorubicin (DOX)-induced kidney damage by reducing oxidative stress and inflammation. PCA pretreatment improved kidney function and antioxidant levels in rats exposed to DOX.
Area of Science:
- Pharmacology
- Toxicology
- Biochemistry
Background:
- Doxorubicin (DOX) is a potent chemotherapy agent known to cause significant toxicity in vital organs, particularly the kidneys.
- DOX-induced nephrotoxicity is characterized by oxidative stress, inflammation, and impaired kidney function.
- Identifying protective agents against DOX-induced organ damage is crucial for improving patient outcomes during chemotherapy.
Purpose of the Study:
- To investigate the protective effects of protocatechuic acid (PCA) against Doxorubicin (DOX)-induced nephrotoxicity in a rat model.
- To evaluate the modulatory impact of PCA on key biomarkers of oxidative stress and inflammation in the kidney.
- To assess the potential of PCA as a therapeutic strategy to mitigate DOX-induced kidney damage.
Main Methods:
- Rats were divided into five groups: control, DOX-induced nephrotoxicity, and three groups pretreated with varying doses of PCA (10 and 20 mg/kg) before DOX administration.
- Biochemical analyses were performed on kidney tissues and serum to measure malondialdehyde (MDA), glutathione (GSH), creatinine, urea, and the activity of antioxidant enzymes (SOD, CAT, GPx, GST).
- Expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) were assessed, alongside histopathological examination of kidney tissues.
Main Results:
- DOX administration significantly increased MDA levels, iNOS and COX2 expressions, and serum creatinine and urea, while decreasing GSH levels and antioxidant enzyme activities in the kidney.
- Pretreatment with PCA (10 and 20 mg/kg) significantly reduced MDA, modulated iNOS and COX2, improved kidney function markers, and restored antioxidant enzyme activities.
- Histopathological analysis confirmed that PCA pretreatment ameliorated DOX-induced kidney tissue damage.
Conclusions:
- Protocatechuic acid (PCA) exhibits significant anti-inflammatory and antioxidative properties.
- PCA demonstrates a protective effect against Doxorubicin (DOX)-induced nephrotoxicity in rats.
- PCA holds potential as a therapeutic agent to mitigate chemotherapy-induced kidney damage.
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