Correction to: α-Phellandrene attenuates tissular damage, oxidative stress, and TNF-α levels on acute model ifosfamide-induced hemorrhagic cystitis in mice.

The published online version contains figure in poor quality.

α-Phellandrene attenuates tissular damage, oxidative stress, and TNF-α levels on acute model ifosfamide-induced hemorrhagic cystitis in mice.

Hemorrhagic cystitis (HC) is the major dose-limiting adverse effect of the clinical use ifosfamide (IFOS). The incidence of this side effect can be as high as 75%. Mesna has been used to reduce the risk of HC, although 5% of patients who get IFOS treatment may still suffer from HC. In previous studies, our group demonstrated that α-phellandrene (α-PHE) possesses anti-inflammatory activity, which opens the door for its study in the attenuation of HC. The objective of this study was to investigate the potential uroprotective effect of the α-PHE in the mouse model of IFOS-induced HC. In order to analyze the reduction of the urothelial damage, the bladder wet weight, hemoglobin content, and the Evans blue dye extravasation from the bladder matrix were evaluated. To investigate the involvement of neutrophil migration and lipid peroxidation and involvement of enzymatic and endogenous non-enzymatic antioxidants, the tissue markers myeloperoxidase (MPO), malondialdehyde, nitrite/nitrate (NOx), superoxide dismutase (SOD), and reduced glutathione (GSH) were evaluated. TNF-α and IL-1ß were measured by ELISA immunoassay technique. The results show that pretreatment with α-PHE significantly reduced urothelial damage that was accompanied by a decrease in the activity of MPO, MDA, and NOx levels and prevention of the depletion of SOD and GSH in bladder tissues. In the assessment of cytokines, α-PHE was able to significantly reduce TNF-α level. However, it does not affect the activities of IL-1ß. These data confirm that α-PHE exerts potent anti-inflammatory properties and demonstrates that α-PHE represents a promising therapeutic option for this pathological condition.

Lack of evidence for regulation of cardiac P-type ATPases and MAP kinases in transgenic mice with cardiac-specific overexpression of constitutively active á1B-adrenoceptors

The regulatory function of á1B-adrenoceptors in mammalian heart homeostasis is controversial. The objective of the present study was to characterize the expression/activity of key proteins implicated in cardiac calcium handling (Na+/K+-ATPase and Ca2+-ATPases) and growth (ERK1/2, JNK1/2 and p38) in mice with cardiac-selective overexpression of constitutively active mutant á1B-adrenoceptor (CAMá1B-AR), which present a mild cardiac hypertrophy phenotype. Immunoblot assays showed that myocardial plasma membrane Ca2+-ATPase (PMCA) expression was increased by 30 percent in CAMá1B-AR mice (N = 6, P < 0.05), although there was no change in sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2) expression. Moreover, total Ca2+-ATPase activity was not modified, but a significant increase in the activity of the thapsigargin-resistant (PMCA) to thapsigargin-sensitive (SERCA) ratio was detected. Neither Na+/K+-ATPase activity nor the expression of á1 and á2 subunit isoforms was changed in CAMá1B-AR mouse hearts. Moreover, immunoblot assays did not provide evidence for an enhanced activation of the three mitogen-activated protein kinases studied in this stage of hypertrophy. Therefore, these findings indicate that chronic cardiac á1B-AR activation in vivo led to mild hypertrophy devoid of significant signs of adaptive modifications concerning primary intracellular calcium control and growth-related proteins, suggesting a minor pathophysiological role of this adrenergic receptor in mouse heart at this stage of development.

Lack of evidence for regulation of cardiac P-type ATPases and MAP kinases in transgenic mice with cardiac-specific overexpression of constitutively active alpha(1B)-adrenoceptors.

The regulatory function of alpha(1B)-adrenoceptors in mammalian heart homeostasis is controversial. The objective of the present study was to characterize the expression/activity of key proteins implicated in cardiac calcium handling (Na(+)/K(+)-ATPase and Ca(2+)-ATPases) and growth (ERK1/2, JNK1/2 and p38) in mice with cardiac-selective overexpression of constitutively active mutant alpha1B-adrenoceptor (CAMalpha(1B)-AR), which present a mild cardiac hypertrophy phenotype. Immunoblot assays showed that myocardial plasma membrane Ca(2+)-ATPase (PMCA) expression was increased by 30% in CAMalpha(1B)-AR mice (N = 6, P < 0.05), although there was no change in sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA2) expression. Moreover, total Ca(2+)-ATPase activity was not modified, but a significant increase in the activity of the thapsigargin-resistant (PMCA) to thapsigargin-sensitive (SERCA) ratio was detected. Neither Na(+)/K(+)-ATPase activity nor the expression of alpha(1) and alpha(2) subunit isoforms was changed in CAMalpha(1B)-AR mouse hearts. Moreover, immunoblot assays did not provide evidence for an enhanced activation of the three mitogen-activated protein kinases studied in this stage of hypertrophy. Therefore, these findings indicate that chronic cardiac alpha(1B)-AR activation in vivo led to mild hypertrophy devoid of significant signs of adaptive modifications concerning primary intracellular calcium control and growth-related proteins, suggesting a minor pathophysiological role of this adrenergic receptor in mouse heart at this stage of development.