The Neuro-Protective Effects of Carnosic Acid in Methotrexate-Induced Neurotoxicity in Male Wistar Rats

Methotrexate (MTX) is a widely used chemotherapeutic agent known for its efficacy
in treating various cancers and autoimmune disorders. However, its use is often
limited by significant neurotoxic side effects, leading to cognitive impairment and
decreased quality of life in patients. This study investigates the neuroprotective
potential of carnosic acid (CA), a natural compound found in rosemary, in mitigating
MTX-induced neurotoxicity.
In vivo experiments were conducted using male Wistar rats to assess the impact of
carnosic acid on MTX-induced neurotoxicity. The animals were divided into four
groups: Control, MTX-treated, low-dose CA (LCA) with MTX, and high-dose CA
(HCA) with MTX. Biochemical assays and behavioral tests were performed to
evaluate neuroinflammation, oxidative stress, and cognitive function.
Results showed that MTX treatment significantly increased serum tumor necrosis
factor-alpha (TNF-α) levels and brain acetylcholinesterase (AChE) activity, while
decreasing serum interleukin-10 (IL-10) levels. These changes indicate increased
inflammation and potential cognitive impairment. Carnosic acid treatment,
particularly at high dose, effectively ameliorated these MTX-induced changes. CA
lowered serum TNF-α levels, increased IL-10 levels, and normalized brain AChE
activity. Moreover, behavioral tests using the Open field test demonstrated that CA
treatment improved spontaneous alternation performance (SAP), suggesting enhanced
cognitive function.
These findings contribute to the understanding of carnosic acid's neuroprotective
properties, highlighting its potential to alleviate MTX-induced neurotoxicity and
preserve cognitive function. The study suggests that carnosic acid may act through
anti-inflammatory and antioxidant mechanisms to confer neuroprotection.
Further research is needed to explore the long-term effects, optimal dosages, and
potential clinical applications of carnosic acid in diverse patient populations receiving
methotrexate treatment. This study opens avenues for developing natural, adjunct
therapies to mitigate the neurotoxic side effects of chemotherapy, potentially
improving patient outcomes and quality of life.