The Ameliorative Effects of Ferulic Acid against Methotrexate Induced Testicular Damage in Rats | ||
| Journal of Applied Veterinary Sciences | ||
| Article 6, Volume 10, Issue 4, October 2025, Pages 55-64 PDF (480.55 K) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/javs.2025.408266.1694 | ||
| Author | ||
| Ghada A. Taqa* | ||
| Professor in veterinary pharmacology and toxicology, College of Dentistry , Mosul university , Iraq | ||
| Abstract | ||
| Nociceptive pain due to surgery is associated with discomfort and suffering. Metamizole sodium, though a potent analgesic, has been banned in many countries. The study is aimed at evaluating the analgesic efficacy of metamizole-sodium in castrated indigenous Nigerian dogs using electrocardiography (ECG). Twelve indigenous Nigerian male dogs aged between 6 months and 1 year with a mean body weight of 11.66 ± 1.26 kg undergoing castration were divided into three groups of four (4) animals each (n = 4). Groups A and B were treated with metamizole sodium via intramuscular (I/M) and transdermal routes at 50 mg/kg and 150 mg/kg, respectively. Group C was treated with normal saline 5 mg/kg i.m.Patients were monitored using standard methods for neutrophil count, vital parameters (rectal temperature, respiratory rate, heart rate and blood pressure), and ECG at 10 minutes before, during and at every 6-hour interval of 48 hours post-surgery. The neutrophil count in the intramuscular group (2.91 ± 0.55 × 109 L-1) was relatively lower than in the transdermal (3.54 ± 0.61 × 109 L-1) and control groups (4.41 ± 1.25 × 109 L-1) at 48 h post-surgery. There was no significant difference in the values of vital parameters obtained between the groups. The QRS interval was lower for intramuscular (0.10 ± 0.06 s) and transdermal (0.04 ± 0.00 s) than the control group (0.20 ± 0.16 s) at 18 h post-surgery. The P and T amplitudes were significantly (P < 0.001) higher for the tested groups than the control group during surgery and at 12 h post-surgery, respectively. In conclusion, the administration of metamizole sodium via the transdermal route prevented the side effect of agranulocytosis, evident by the decrease in neutrophil count of the intramuscular group compared to the transdermal group. Metamizole sodium transdermal patch induced analgesia, evident by the increase in QRS interval and decrease in P and T amplitudes of the ECG reading. This may be beneficial in alleviating pain due to castration in Nigerian indigenous dogs.Methotrexate (MTX), an extensively used chemotherapeutic and immunosuppressive agent, is well-documented for its gonadotoxic effects. Ferulic acid (FA), a natural phenolic compound with potent antioxidant properties, has shown protective effects in various organ systems. This study aimed to assess the protective and therapeutic potentials of FA against MTX-induced testicular damage in a rat model. Twenty-four adult male rats were allocated into four groups: control, MTX-only, MTX plus FA (protective), and MTX followed by FA (therapeutic). Testicular tissues were assessed histologically for tubular integrity and germ cell preservation. Histomorphometric parameters, including seminiferous tubule diameter and germinal epithelial height. Also, the level of Caspase-3 expression was analyzed using immunohistochemistry to examine apoptosis activity. The group treated with MTX showed testicular damage and a significant decrease in germ cells along with lower histomorphometric measures and increased Caspase-3 expression levels. On the other hand, both groups treated with FA displayed noticeable improvements in both histology and molecular aspects. The treated group showed normal testicular structure, along with restored histomorphometric values and minimal Caspase-3 expression similar, to the control group. Conclusion: FA successfully reduced the effects of (MTX) in the testicles by maintaining their structure and preventing cell death processes. This suggests that FA could be an addition to protect men’s reproductive health during chemotherapy treatments | ||
| Keywords | ||
| Apoptosis; Ferulic acid; Methotrexate; Oxidative stress; Spermatogenesis; Testicular toxicity | ||
| References | ||
|
BABA, M. A., FAZILI, M. R., and ATHAR, H., 2016. Sonographic alterations in testicles following pinhole castration in dogs. Indian Journal of Veterinary Surgery, 37(1): 19-22. https://agris.fao.org/search/en/providers/122535/records/65df34714c5aef494fe0d824
BALDRIDGE, S. L., COETZEE, J. F., DRITZ, S. S., REINBOLD, J. B., GEHRING, R., HAVEL, J., and KUKANICH, B., 2011. Pharmacokinetics and physiologic effects of intramuscularly administer xylazine hydrochloride-ketamine hydrochloride-butorphanol tartrate alone or in combination with orally administered sodium salicylate on biomarkers of pain in Holstein's calves following castration and dehorning. American Journal of Veterinary Research, 72 (100): 1305-1317. https://doi.org/10.2460/ajvr.72.10.1305
BRENNAN, T. J., ZAHN, P. K., and POGATZKI-ZAHN, E. M., 2005. Mechanisms of Incisional pain. Anaesthesiology Clinics, 23:1-20. https://doi.org/10.1016/j.atc.2004.11.009
CHERUKURI, S., BATCHU, U. R., MANDAVA, K., CHERUKURI, V., and GANAPURAM, K. R., 2017. Formulation and evaluation of transdermal drug delivery of topiramate. International Journal of Pharmaceutical Investigation, 7:10-7. https://doi.org/10.4103/jphi.JPHI_35_16
CHU, Y., ZHOA, X., HAN, J., and SU, Y., 2017. Physiological signal-based method for measurement of pain intensity. Frontiers in Neuroscience, 11:279. https://doi.org/10.3389/fnins.2017.00279
COETZEE, J. F., LUBBERS, B. L., TOERBER, S. E., GEHRING, R., THOMSON, D.U., WHITE, B. J., and Apley, M. D., 2008. Plasma concentration substance p and cortisol in beef calves after castration or stimulated castration. American Journal of Veterinary Research, 69(6): 751-7 62. https://doi.org/10.2460/ajvr.69.6.751
COETZEE, J. F., 2011. A review of pain assessment technique and pharmacological approaches to pain relief after bovine castration: Practical implication for cattle production within the United States. Applied Animal Behaviour Science, 135: 192-213. https://doi.org/10.1016/j.applanim.2011.10.016.
COETZEE, J.F., 2013. Assesement and management of pain associated with castration in cattle. Veterinary Clinics of North America: Food Animal practice Journal. https://doi.org/10.1016/j.cvfa.2012.11.002
COHEN, L. L., LA GRECA, A. M., BLOUNT, R. L., KAZAK, A. E., and HOLMBECK, G. N., 2008. Introduction to special Issue: Evidence-based assessment in paediatric psychology. Journal of Paediatric Psychology, 33: 911–915.https://doi.org/10.1093/jpepsy/jsj115
COHEN, S. P., and MAO, J., 2014. Neuropathic pain: mechanisms and their clinical implications. British Medical Journal. https://doi.org/10.1136/bmj.f7656
DIGANGI, B. A., GRIJALVA, J., JARAMILLO, E. P. P., DUEÑAS, I., GLENN, C., CRUZ, M. E. C., and Pérez, R. P. M., 2017. Post-operative outcomes of surgical and chemical castration with zinc gluconate in dogs presenting to veterinary field clinics. The Veterinary Journal, 229: 26. https://doi.org/10.1016/j.tvjl.2017.10.016
FREEMAN, L. J., FERGUSON, N., FELLENSTEIN, C., JOHNSON, R., and CONSTABLE, P. D., 2017. Evaluation of learning curves for ovariohysterectomy of dogs and cats and castration of dogs. Journal of the American Veterinary Medical Association, 251(3): 322-332. https://doi.org/10.2460/javma.251.3.322
Gaur, P. K., Mishra, S., Purohit, S., and DAVE, K., 2009. Transdermal drug delivery system- A review. Asian Journal of Pharmaceutical and Clinical Research, 2: 14-20.
HUBER, M., ANDERSOHN, F., SARGANAS, G., BRONDER, E., KLIMPEL, A., THOMAS, M., KONZEN, C., KREUTZ, R., and GARBE, E., 2015. Metamizole-induced agranulocytosis revisited: results from the prospective Berlin Case-Control Surveillance Study. European Journal of Clinical Pharmacology, 71(2): 219-227. https://doi.org/10.1007/s00228-014-1777-8
IGNACIO, L., MONTSERRAT, S., MARÍA, A., MARÍA, L. H., CANDELAS, L., MARÍA, D., MÓNIKA, W., and JULIA, D., 2015. Validation of the behavioural indicators of pain scale ESCID for pain assessment in non-communicative and mechanically ventilated critically ill patients: a research protocol. Journal of Advanced Nursing, 72(1): 205-216. https://doi.org/10.1111/jan.12808
KAUFMANN, C. A., FORNDRAN, S., STAUBER, C., WOERNER, K., and GANSLOßER, U., 2017. The social behaviour of neutered male dogs compared to intact dogs (Canis lupus familiaris): Video analyses, questionnaires and case studies. Veterinary Medical Open Journal, 2(1): 22-37.
MCMEEKAN, C. M., STAFFORD, K. J., MELLOR, D. J., BRUCE, R. A., WARD, R. N., and GREGORY, N. G., 1999. Effect of a local anaesthetic and non-steroidal anti-inflammatory analgesic on the acute cortisol response of calves to dehorning. New Zealand Veterinary Journal, 47: 92 -96. https://doi.org/10.1080/00480169.1999.36120.
NIKOLOVA, I., TENCHEVA, J., VOINIKOV, J., PETKOVA, V., BENBASAT, N., and DANCHEV, N., 2012. Metamizole: a review profile of a well-known “forgotten” drug. Part I: pharmaceutical and nonclinical profile. Biotechnology and Biotechnological Equipment, 26(6): 3329-3337. https://doi.org/10.5504/BBEQ.2012.0089
NIMESH, G., and PARESH, P., 2016. Formulation development and evaluation of matrix-type lidocaine topical patch for local anaesthetic. International Journal of Research and Development in Pharmacy and Life Sciences, 5(1): 1963-1973.
OMKAR N. G., and SANTHOSH K. N., 2018. Effect of mental stress on autonomic nervous function in young adults. Indian Journal of Clinical Anatomy and Physiology, 5(1): 47-51. https://doi.org/10.18231/2394-2126.2018.0012
PASCALE, R., SIMON, A., MARTIN, G., JÉRÔME, R. E. D., DAPHNÉE, V., DIANE, F., DOMINIQUE, G., and ERIC, T., 2012. Validation of orthopaedic postoperative pain assessment methods for dogs: A prospective, blinded, randomised, placebo-controlled study. PLoS One, 7(11): 49480- 49481. https://doi.org/10.1371/journal.pone.0049480
PRAUSNITZ, M. R., and LANGER, R., 2011. Transdermal drug delivery. Natural Biotechnology, 26(11): 1261–1268. https://doi.org/10.1038/nbt.1504
REID, J., NOLAN, A. M., HUGHES, J. M. L., LASCELLES, D., and PAWSON, P., 2007. Development of the short-form Glasgow composite measure pain scale (CMPS-SF) and derivation of an analgesic intervention score. Animal welfare, 16: 97–104. https://doi.org/10.1017/S096272860003178X
RITESH, B., and RENI, K., 2015. Transdermal drug delivery system: formulation, development and evaluation - An overview. International Journal of Biomedical and Advance Research, 6(1): 1-10. https://doi.org/10.7439/ijbar.v6i1.1556
SINGH. V. K., POKHARIYAL, T., and TIWARI A. K., 2013. Transdermal drug delivery system for non-steroidal anti-inflammatory drugs: A review. Indo-American Journal of Pharmaceutical Research, 3(5): 3588-3605
SNELL, W. L., ORSHER, R. J., LARENZA-MENZIES, M. P., and POPOVITCH, C. A., 2015. Comparison of caudal and pre-scrotal castration for management of perineal hernia in dogs between 2004 and 2014. New Zealand Veterinary Journal, 63(5): 272-275. https://doi.org/10.1080/00480169.2015.1023858
HIE, B. J., COETZEE, J. F., RENTER, D. G., BABCOCK, A. H., THOMSON, D. U., and ANDRESEN, D., 2008. Evaluation of two-dimensional accelerometers to monitor behavior of beef calves after castration. American Journal of Veterinary Research, 69(8): 1005-1012. https://doi.org/10.2460/ajvr.69.8.1005
XU, J, and BRENNAN, T. J., 2009. Comparison of skin incision vs. skin plus deep tissue incision on ongoing pain and spontaneous activity in dorsal horn neurons. Pain, 144: 329–339. https://doi.org/10.1016/j.pain.2009.05.019
| ||
|
Statistics Article View: 117 PDF Download: 108 |
||
