Low quality of life and life-threatening conditions often demand pharmacological screening of lead compounds. A spectrum of pharmacological activities has been attributed to pyrazole analogs. The substitution, replacement, or removal of functional groups on a pyrazole ring appears consistent with diverse molecular interactions, efficacy, and potency of these analogs. This mini-review explores cytotoxic, cytoprotective, antinociceptive, anti-inflammatory, and antidepressant activities of some pyrazole analogs to advance structure-related pharmacological profiles and rational design of new analogs. Numerous interactions of these derivatives at their targets could impact future research considerations and prospects while offering opportunities for optimizing therapeutic activity with fewer adverse effects.

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Despite being involved in homeostatic control and hydro-electrolyte balance, the contribution of medullary (A1 and A2) noradrenergic neurons to the hypertonic saline infusion (HSI)-induced cardiovascular response after hypotensive hemorrhage (HH) remains to be clarified. Hence, the present study sought to determine the role of noradrenergic neurons in HSI-induced hemodynamic recovery in male Wistar rats (290–320 g) with HH. Medullary catecholaminergic neurons were lesioned by nanoinjection of antidopamine-β-hydroxylase–saporin (0.105 ng·nl−1) into A1, A2, or both (LES A1; LES A2; or LES A1+A2, respectively). Sham rats received nanoinjections of free saporin in the same regions (SHAM A1; SHAM A2; or SHAM A1+A2, respectively). After 15 days, rats were anesthetized and instrumented for cardiovascular recordings. Following 10 min of stabilization, HH was performed by withdrawing arterial blood until mean arterial pressure (MAP) reaches 60 mmHg. Subsequently, HSI was performed (NaCl 3 M; 1.8 ml·kg−1, i.v.). The HH procedure caused hypotension and bradycardia and reduced renal, aortic, and hind limb blood flows (RBF, ABF, and HBF). The HSI restored MAP, heart rate (HR), and RBF to baseline values in the SHAM, LES A1, and LES A2 groups. However, concomitant A1 and A2 lesions impaired this recovery, as demonstrated by the abolishment of MAP, RBF, and ABF responses. Although lesioning of only a group of neurons (A1 or A2) was unable to prevent HSI-induced recovery of cardiovascular parameters after hemorrhage, lesions of both A1 and A2 made this response unfeasible. These findings show that together the A1 and A2 neurons are essential to HSI-induced cardiovascular recovery in hypovolemia. By implication, simultaneous A1 and A2 dysfunctions could impair the efficacy of HSI-induced recovery during hemorrhage.

Perturbations to nutrition during critical periods are associated with changes in embryonic, fetal or postnatal developmental patterns that may render the offspring more likely to develop cardiovascular disease in later life. The aim of this study was to evaluate whether autonomic nervous system imbalance underpins in the long-term hypertension induced by dietary protein restriction during peri-pubertal period. Male Wistar rats were assigned to groups fed with a low protein (4% protein, LP) or control diet (20.5% protein; NP) during peri-puberty, from post-natal day (PN) 30 until PN60, and then all were returned to a normal protein diet until evaluation of cardiovascular and autonomic function at PN120. LP rats showed long-term increased mean arterial pressure (p = 0.002) and sympathetic arousal; increased power of the low frequency (LF) band of the arterial pressure spectral (p = 0.080) compared with NP animals. The depressor response to the ganglion blocker hexamethonium was increased in LP compared with control animals (p = 0.006). Pulse interval variability showed an increase in the LF band and LF/HF ratio (p = 0.062 and p = 0.048) in LP animals. The cardiac response to atenolol and/or methylatropine and the baroreflex sensitivity were similar between groups. LP animals showed ventricular hypertrophy (p = 0.044) and increased interstitial fibrosis (p = 0.028) compared with controls. Reduced protein carbonyls (PC) (p = 0.030) and catalase activity (p = 0.001) were observed in hearts from LP animals compared with control. In the brainstem, the levels of PC (p = 0.002) and the activity of superoxide dismutase and catalase (p = 0.044 and p = 0.012) were reduced in LP animals, while the levels of GSH and total glutathione were higher (p = 0.039 and p = 0.038) compared with NP animals. Protein restriction during peri-pubertal period leads to hypertension later in life accompanied by sustained sympathetic arousal, which may be associated with a disorganization of brain and cardiac redox state and structural cardiac alteration.

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The aim of this work is to evaluate the renal function and the morphology of the kidneys inthe offspring, of both sexes, of mothers who underwent a 50% food restriction duringlactation. Pregnant Wistar rats were divided into two experimental groups: Control group(CO) fed with standard diet and Food restriction (FR) fed with standard diet restricted to 50%of the daily food intake of CO mothers. The intervention was carried out from the 1st to the14th day of lactation, after from the 14th to the 21st day of lactation. The offspring of bothgroups were fed with standard diet and water ad libitum until 120-day-old. At the end of theexperimental period 24-hour urine collection was performed. After euthanasia biochemicaland histological analysis were performed. Male and female FR offspring showed no change inbody weight or kidney weight compared to control counterparts. Male FR showed a reductionin the glomerular filtration rate (CO 3.22±0.35 vs FR 2.25±0.12; ml/min) and increased totalurinary protein (CO 82.82±11.79 vs FR 123.8±8.37; mg/dL) compared to the CO offspring.We observed a reduction in glomerular area in the male FR (CO 7259±271.7 vs FR6349±106.3; μm 2 ) in comparison to CO offspring. In conclusion, maternal food restrictioncauses functional and morphological kidney damage in adult males, being a sex-specificresponse since females did not show alterations.

GHSr signaling is involved in the regulation of energy homeostasis. LEAP2, a recentlydiscovered peptide hormone, counteracts the effects of ghrelin. This study sought to evaluatethe effects of perinatal LEAP2 exposure in young rat offspring. For this, two protocols weredesigned to assess the roles of GHSr antagonism during the pregnancy and during thelactation. Sex-specific impacts on AUC and peak-responses of glucose tolerance tests werepresented. However, no differences were detected in the blood glucose of mixed meal fedanimals. In conclusion, perinatal LEAP2 exposure could impact the glucose-stimulatedinsulin secretion in young rats.

Nicotine is one of the main psychoactive and toxic substances found in tobacco and itsexposure during the postnatal period can cause several damages to the health of the childduring intrauterine development and in adult life. The aim of this study was to evaluate theeffect of maternal postnatal nicotine exposure on cardiac parameters in adult rat offspring.Weight monitoring, echocardiography and organ collections were performed. In conclusion,offspring from mothers exposed to nicotine develops cardiac hypertrophy, further maleoffspring were more affected.