Tilmicosin (TIL) is a common macrolide antibiotic in veterinary medicine. High doses of
TIL can have adverse cardiovascular effects. This study examined the effects of Rhodiola rosea (RHO)
that have anti-inflammatory, antioxidant, and anti-fibrotic effects on tilmicosin (TIL)-induced cardiac
injury targeting anti-inflammatory, antioxidant, apoptotic, and anti-apoptotic signaling pathways
with anti-fibrotic outcomes. Thirty-six maleWistar albino rats were randomly divided into groups
of six rats each. Rats received saline as a negative control, CARV 1 mL orally (10 mg/kg BW), and
RHO 1 mL orally at 400 mg/kg BW daily for 12 consecutive days. The TIL group once received a
single subcutaneous injection (SC) dose of TIL (75 mg/kg BW) on the sixth day of the experiment to
induce cardiac damage. The standard group (CARV + TIL) received CARV daily for 12 consecutive
days with a single TIL SC injection 1 h after CARV administration only on the sixth day of study
and continued for another six successive days on CARV. The protective group (RHO + TIL) received
RHO daily for the same period as in CARV + TIL-treated rats and with the dosage mentioned
before. Serum was extracted at the time of the rat’s scarification at 13 days of study and examined
for biochemical assessments in serum lactate dehydrogenase (LDH), cardiac troponin I (cTI), and
creatine phosphokinase (CK-MB). Protein carbonyl (PC) contents, malondialdehyde (MDA), and
total antioxidant capacity (TAC) in cardiac homogenate were used to measure these oxidative stress
markers. Quantitative RT-PCR was used to express interferon-gamma (INF-
), cyclooxygenase-2
(COX-2), OGG1, BAX, caspase-3, B-cell lymphoma-2 (Bcl-2), and superoxide dismutase (SOD) genes in
cardiac tissues, which are correlated with inflammation, antioxidants, and apoptosis. Alpha-smooth
muscle actin (-SMA), calmodulin (CaMKII), and other genes associated with Ca2+ hemostasis
and fibrosis were examined using IHC analysis in cardiac cells (myocardium)