Treatment of dilated cardiomyopathy caused by coronary microvascular dysfunction with anisodamine: a report of 5 cases.

The management of dilated cardiomyopathy (DCM) is well established. However, a subset of patients does not have recovery from or have recurrences of left ventricular (LV) dysfunction despite receiving optimal medical therapy. Coronary microvascular dysfunction (CMD) can result from structural and functional abnormalities at the intramural and small coronary vessel level affecting coronary blood flow autoregulation and consequently leading to impaired coronary flow reserve. Dilated myocardial phenotype may be responsible for CMD in DCM. Anisodamine can exert a significant effect on relieving microvascular spasm, and improving and dredging the coronary microcirculation. However, whether CMD can be potentially improved with anisodamine to make DCM better remains incompletely understood.

Effect of intracoronary agents on the no-reflow phenomenon during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction: a network meta-analysis.

BACKGROUND: Despite the restoration of epicardial flow after primary percutaneous coronary intervention (PPCI), myocardial reperfusion remains impaired in a significant proportion of patients. We performed a network meta-analysis to assess the effect of 7 intracoronary agents (adenosine, anisodamine, diltiazem, nicorandil, nitroprusside, urapidil, and verapamil) on the no-reflow phenomenon in patients with ST-elevation myocardial infarction (STEMI) undergoing PPCI. METHODS: Database searches were conducted to identify randomized controlled trials (RCTs) comparing the 7 agents with each other or with standard PPCI. Outcome measures included thrombolysis in myocardial infarction flow grade (TFG), ST-segment resolution (STR), left ventricular ejection fraction (LVEF), major adverse cardiovascular events (MACEs), and adverse events. RESULTS: Forty-one RCTs involving 4069 patients were analyzed. The addition of anisodamine to standard PPCI for STEMI was associated with improved post-procedural TFG, more occurrences of STR, and improvement of LVEF. The cardioprotective effect of anisodamine conferred a MACE-free survival benefit. Additionally, nitroprusside was regarded as efficient in improving coronary flow and clinical outcomes. Compared with standard care, adenosine, nicorandil, and verapamil improved coronary flow but had no corresponding benefits regarding cardiac function and clinical outcomes. The ranking probability for the 7 treatment drugs showed that anisodamine consistently ranked the highest in efficacy outcomes (TFG < 3, STR, LVEF, and MACEs). No severe adverse events, such as hypotension and malignant arrhythmia, were observed in patients treated with anisodamine. Network meta-regression analysis showed that age, the time to reperfusion, and study follow-up did not affect the treatment effects. CONCLUSIONS: The intracoronary administration of anisodamine appears to improve myocardial reperfusion, cardiac function, and clinical outcomes in patients with STEMI undergoing PPCI. Given the limited quality and quantity of the included studies, more rigorous RCTs are needed to verify the role of this inexpensive and well-tolerated regimen.

Combined administration of anisodamine and neostigmine rescued acute lethal crush syndrome through α7nAChR-dependent JAK2-STAT3 signaling.

Previously we showed that Ani (anisodamine)/Neo (neostigmine) combination produced anti-shock effect via activating α7 nicotinic acetylcholine receptor (α7nAChR). In this study, we aim to investigate the therapeutic effect and underlying mechanisms of Ani/Neo combination in acute lethal crush syndrome (CS). In rat and rabbit CS models, Ani/Neo combination increased the 24 h survival rates, improved hemodynamics and decreased the levels of creatine kinase, MB isoenzyme of creatine kinase, blood urea nitrogen, creatinine, K+ in serum. It also decreased the levels of H2O2, myeloperoxidase (MPO) and nitric oxide (NO) in serum and compressed muscle in rat CS model. In wild-type (WT) mice with CS, Ani/Neo combination increased 24 h survival rate and decreased the levels of H2O2, MPO, NO, TNFα, IL-6 and IL-10 in compressed muscle. These effects were attenuated by α7nAChR knockout (KO). Moreover, Ani/Neo combination prevented the decrease of phosphorylation of Janus kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 (STAT3) induced by CS. These effects of Ani/Neo in CS mice were cancelled by methyllycaconitine (α7nAChR antagonist) and α7nAChR KO. Collectively, our results demonstrate that Ani/Neo combination could produce therapeutic effects in CS. The underlying mechanism involves the activation of α7nAChR-dependent JAK2-STAT3 signaling pathway.

Inactivation of PI3-K/Akt and reduction of SP1 and p65 expression increase the effect of solamargine on suppressing EP4 expression in human lung cancer cells.

BACKGROUND: Lung cancer is the most common cause of cancer-related deaths worldwide. Natural phytochemicals from traditional medicinal plants such as solamargine have been shown to have anticancer properties. The prostaglandin E2 receptor EP4 is highly expressed in human cancer, however, the functional role of EP4 in the occurrence and progression of non small cell lung cancer (NSCLC) remained to be elucidated. METHODS: Cell viability was measured by MTT assays. Western blot was performed to measure the phosphorylation and protein expression of PI3-K downstream effector Akt, transcription factors SP1, p65, and EP4. Quantitative real-time PCR (qRT-PCR) was used to examine the mRNA levels of EP4 gene. Exogenous expression of SP1, p65, and EP4 genes was carried out by transient transfection assays. EP4 promoter activity was measured by Dual Luciferase Reporter Kit. RESULTS: We showed that solamargine inhibited the growth of lung cancer cells. Mechanistically, we found that solamargine decreased the phosphorylation of Akt, the protein, mRNA expression, and promoter activity of EP4. Moreover, solamargine inhibited protein expression of SP1 and NF-κB subunit p65, all of which were abrogated in cells transfected with exogenous expressed Akt. Intriguingly, exogenous expressed SP1 overcame the effect of solamargine on inhibition of p65 protein expression, and EP4 protein expression and promoter activity. Finally, exogenous expressed EP4 feedback reversed the effect of solamargine on phosphorylation of Akt and cell growth inhibition. CONCLUSION: Our results show that solamargine inhibits the growth of human lung cancer cells through inactivation of Akt signaling, followed by reduction of SP1 and p65 protein expression. This results in the inhibition of EP4 gene expression. The cross-talk between SP1 and p65, and the positive feedback regulatory loop of PI3-K/Akt signaling by EP4 contribute to the overall responses of solamargine in this process. This study unveils a novel mechanism by which solamargine inhibits growth of human lung cancer cells.

A functional drug delivery platform for targeting and imaging cancer cells based on Pluronic F127.

Functional polymeric micelles play an important role in the efficient delivery of therapeutic drugs into tumours. In this study, a functional drug delivery platform with ligands for targeting and fluorescent imaging was designed based on Pluronic F127 (PF127). Using folic acid (FA) and fluorescein isothiocyanate (FITC) to chemically conjugate with PF127, two functional polymers, Pluronic F127-FA (PF127-FA) and Pluronic F127-FITC (PF127-FITC), were synthesized. Solasodine-loaded micelles were then prepared via the thin-film hydration method. By employing A549 and HeLa cells, the results of in vitro cell assays performed using confocal laser scanning microscopy and flow cytometry suggested that the proposed micelles could provide the desired specific targeting and fluorescent imaging functions. In addition, the results of in vitro cytotoxicity experiments showed that the growth inhibition rates of A549 and HeLa cells treated with solasodine-loaded micelles were remarkably higher than those of cells treated with free solasodine. Solasodine-loaded micelles exhibited a more distinct inhibitory effect against HeLa cells than against A549 cells. Thus, an effective drug delivery system for targeting and imaging cancer cells was developed.

Effects of combined anisodamine and neostigmine treatment on the inflammatory response and liver regeneration of obstructive jaundice rats after hepatectomy.

BACKGROUND: Cholestasis is associated with high rates of morbidity and mortality in patients undergoing major liver resection. This study aimed to evaluate the effects of a combined anisodamine and neostigmine (Ani+Neo) treatment on the inflammatory response and liver regeneration in rats with obstructive jaundice (OJ) after partial hepatectomy. MATERIALS AND METHODS: OJ was induced in the rats by bile duct ligation. After 7 days biliary drainage and partial hepatectomy were performed. These rats were assigned to a saline group or an Ani+Neo treatment group. The expressions of inflammatory mediators, liver regeneration, and liver damage were assessed at 48 h after hepatectomy. RESULTS: The mRNA levels of TNF-α, IL-1ß, IL-6, MCP-1, and MIP-1α, in the remnant livers, and the serum levels of TNF-α and IL-1ß were substantially reduced in the Ani+Neo group compared with saline group (P<0.05). The Ani+Neo treatment obviously promoted liver regeneration as indicated by the liver weights and Ki-67 labeling index (P<0.05). The serum albumin and γ-GT levels and liver neutrophil infiltration also significantly improved in the Ani+Neo group (P<0.05) compared with the saline group. CONCLUSIONS: These results demonstrate that the combined anisodamine and neostigmine treatment is able to improve the liver regeneration in rats with OJ by substantially alleviating the inflammatory response.

In vitro and in vivo evaluation of the delivery of topical formulations containing glycoalkaloids of Solanum lycocarpum fruits.

The glycoalkaloids solasonine (SN) and solamargine (SM) have been studied for their antiparasitic, antifungal, and anticancer properties, especially in vitro and in vivo against non-melanoma skin cancer. Thus, the alkaloidic extract of Solanum lycocarpum, which contains approximately 45% each of SN and SM, was used to define the best experimental conditions for in vitro and in vivo assays. The in vitro assays were performed with the Franz cell diffusion porcine skin model to evaluate the effects of different pHs and the presence of monoolein, ethoxydiglycol or ethanol penetration enhancers on the skin penetration and retention of SN and SM after 3, 6, 9 and 12h of exposure. The in vivo assay was performed on hairless mice with the formulation selected in the in vitro assays. The results showed that pH 6.5 was optimal for SM penetration. The formulation containing 5% alkaloidic extract, 5% propylene glycol, 5% monoolein and a hydroxyethyl cellulose gel base (Natrosol) (pH 6.5) was optimal for the delivery of SN and SM into the skin, and this formulation is potentially useful for the topical therapy of several skin disorders.

Anisodamine accelerates spontaneous passage of single symptomatic bile duct stones ≤ 10 mm.

AIM: To investigate the rate of spontaneous passage of single and symptomatic common bile duct (CBD) stones ≤ 10 mm in diameter in 4 wk with or without a 2-wk course of anisodamine. METHODS: A multicenter, randomized, placebo-controlled trial was undertaken. A total of 197 patients who met the inclusion criteria were enrolled. Ninety-seven patients were assigned randomly to the control group and the other 100 to the anisodamine group. The anisodamine group received intravenous infusions of anisodamine (10 mg every 8 h) for 2 wk. The control group received the same volume of 0.9% isotonic saline for 2 wk. Patients underwent imaging studies and liver-function tests every week for 4 wk. The rate of spontaneous passage of CBD stones was analyzed. RESULTS: The rate of spontaneous passage of CBD stones was significantly higher in the anisodamine group than that in the control group (47.0% vs 22.7%). Most (87.2%, 41/47) stone passages in the anisodamine group occurred in the first 2 wk, and passages in the control group occurred at a comparable rate each week. Factors significantly increasing the possibility of spontaneous passage by univariate logistic regression analyses were stone diameter (< 5 mm vs ≥ 5 mm and ≤ 10 mm) and anisodamine therapy. Multivariate logistic regression analyses revealed that these two factors were significantly associated with spontaneous passage. CONCLUSION: Two weeks of anisodamine administration can safely accelerate spontaneous passage of single and symptomatic CBD stones ≤ 10 mm in diameter, especially for stones < 5 mm.

Combined administration of anisodamine and neostigmine produces anti-shock effects: involvement of α7 nicotinic acetylcholine receptors.

AIM: To evaluate the anti-effects of anisodamine and neostigmine in animal models of endotoxic and hemorrhagic shock. METHODS: Kunming mice were injected with lipopolysaccharide (LPS 30 mg/kg, ip) to induce endotoxic shock. Anisodamine (12.5, 25, and 50 mg/kg, ip) and neostigmine (12.5, 25, and 50 µg/kg, ip) were administered immediately after LPS injection. Survival rate was monitored, and the serum levels of TNF-α and IL-1ß were analyzed using ELISA assays. The effects of anisodamine and neostigmine were also examined in α7 nicotinic acetylcholine receptor (α7 nAChR) knockout mice with endotoxic shock and in Beagle dogs with hemorrhagic shock. RESULTS: In mice with experimental endotoxemia, combined administration of anisodamine and neostigmine significantly increased the survival rate and decreased the serum levels of inflammatory cytokines, as compared to those produced by either drug alone. The anti-shock effect of combined anisodamine and neostigmine was abolished in α7 nAChR knockout mice. On the other hand, intravenous injection of the combined anisodamine and neostigmine, or the selective α7 nAChR agonist PNU282987 exerted similar anti-shock effects in dogs with hemorrhagic shock. CONCLUSION: The results demonstrate that combined administration of anisodamine and neostigmine produces significant anti-shock effects, which involves activation of α7 nAChRs.

Prenatal exposure to tobacco extract containing nicotinic alkaloids produces morphological and behavioral changes in newborn rats.

Tobacco exposure is not only a health concern for adults but has also been shown to exert deleterious effects on the health of the fetus, newborn, child, and adolescent. Decreased cognitive function, lower Intellectual Quotient (IQ) and deficits in learning and memory in children have been associated with maternal smoking during pregnancy. In this study, we have studied the effect of a tobacco plant extract on the growth and development in the rat. The extract contained relative proportions of alkaloids, including nicotine, purified by chemical separation. Pregnant rats received oral doses of either control (NaCl) or tobacco extract during the entire gestational period. Offspring length and body weight were measured. Each day, the offspring were observed for the following physical parameters: hair growth, incisor eruption and eye opening. The day of appearance of these developments was recorded. Before weaning, the offspring were examined to test their cliff avoidance response (6 postnatal day (PN)), surface righting reflex (05, 07, 13 postnatal day), swimming development (10, 12 postnatal day), negative geotaxis response (7,9,13 and 17 postnatal day) and jumping down choice cage (15, 17 postnatal day). Administration of tobacco extract to dams during the entire gestation period affects behavior and development in pups. The observed effects were a delay in opening eyes, incisor eruption and hair appearance, behavioral developments and an alteration in the rate of success behavior. However, in the jumping down choice cage test there was no difference compared to control animals. The results suggest that tobacco extract has a significant effect on the development of behavioral patterns, orientation and motor coordination and function. They also suggest significant growth retardation and teratogenic effects.

Modulatory effect of anisodamine on airway hyper-reactivity and eosinophilic inflammation in a murine model of allergic asthma.

Anisodamine, a peripheral muscarinic receptor antagonist, is a naturally occurring atropine derivative that has been isolated, synthesized and characterized by scientists in China. In the present investigation, we evaluated the modulatory effects of anisodamine on airway hyper-reactivity and inflammation in a murine model of allergic asthma. Asthma model was induced successfully by ovalbumin. The activation of cells, airway eosinopilia, cytokine production, and airway function were examined. Our results collectively show that anisomanine could significantly suppress the accumulation of eosinophils into the airways and dramatically inhibited the histological changes in OVA-induced mice. Additionally, anisodamine could restore the Th1/Th2 balance in BALF by downregulating the level of Th2 cell-associated cytokine IL-4 (p<0.01) and upregulating the level of Th1 cell-associated cytokine IFN-γ (p<0.01). In addition, pretreatment with anisodamine also showed strong suppression of allergen-induced bronchial hyper-reactivity with maximum contraction decreasing from 0.45 ± 0.02 g to 0.28 ± 0.03 g (p<0.01). These results suggested the modulatory effects of anisodamine on Th1/Th2 balance by enhancing Th1-related and suppressing Th2-related parameters, as well as its potential application in airway hyper-reactivity and eosinophilic inflammation.

Anticonvulsant activity of solasodine isolated from Solanum sisymbriifolium fruits in rodents.

CONTEXT: Solanum sisymbriifolium Lam. (Solanaceae), commonly known as sticky nightshade, is traditionally used for central nervous system (CNS) disorders. Although solasodine has been isolated from this plant, little is known about its anticonvulsant and CNS depressant actions. OBJECTIVE: We investigated anticonvulsant and CNS depressant effects of solasodine isolated from S. sisymbriifolium using several experimental models. MATERIALS AND METHODS: Swiss albino mice (n=6) were employed for pentylenetetrazole (PTZ) and picrotoxin (PCT)-induced convulsions and thiopental-induced sleep time. Different groups of Wistar albino rats (n=6) were subjected to maximal electroshock (MES) test. Solasodine, a steroidal glycoalkaloid, was isolated from dried fruits of S. sisymbriifolium and identified by GC-MS. RESULTS: The results showed that intraperitoneal (i.p.) injection of solasodine (25 mg/kg) significantly delayed (p < 0.01) latency of hind limb tonic extensor (HLTE) phase in the PCT-induced convulsions. In the MES model, solasodine significantly reduced (p < 0.001) duration of HLTE at 25, 50, and 100 mg/kg, i.p. in a dose-dependent manner. Interestingly, solasodine did not produce any significant reduction in PTZ-induced convulsions. Prior treatment of solasodine (25, 50, and 100 mg/kg, i.p.) significantly potentiated thiopental-provoked sleep in a dose-dependent manner (p < 0.001). DISCUSSION AND CONCLUSION: Our study, for the first time, shows potent anticonvulsant and CNS depressant activities of solasodine. It is likely that solasodine, in part, is responsible for the anticonvulsant and sedative properties of S. sisymbriifolium. The future study should focus on the exact mechanism of action of solasodine.

[Effect of intra-coronary injection of anisodamine on the slow-reflow phenomenon in patients with acute myocardial infarction after percutaneous coronary intervention].

OBJECTIVE: To assess the effect and safety of intra-coronary administration of anisodamine on "slow-reflow" phenomenon of infarct related artery (IRA) following primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). METHODS: Twenty-five patients with slow-reflow phenomenon screened out from 153 AMI patient with post-PCI reflow IRA were enrolled. They were 17 males and 8 females; aged (62.3 +/- 9.3) years; 10 with focal artery at left anterior descendens, 5 in circumflux and 10 in right coronary artery; PCI was successfully performed on them about 7.11 +/- 2.31 h after the onset of angina pectoris and the post-operation mean TIMI flow was 1.75 +/- 0.42 grade. Nitroglycerin (200 microg) was injected into coronary previously for confirming the slow-reflow phenomenon as control, then the injection of anisodamine 500 microg 10 min later. Coronary arteriography (CAG) was performed at the 1 st, 3 rd and 10 th min after the medication. Gibson's TIMI frame count method and quantitative computer angiography (QCA) system was used to quantitatively detect the frames of blood flow and the diameter of arterial lumen at different time points after nitroglycerin or anisodamine administration. Hemodynamics and changes of electrocardiogram were determined. RESULTS: (1) No significant change in frames of blood flow was found between before and 1 min after intra-coronary administration of nitroglycerin (82.79 +/- 9.30 frames vs 78.43 +/- 9.37 frames, P >0. 05) after operation; but 1, 3 and 10 min after injection of anisodamine, it was decreased 46.25 +/- 4.55, 44.52 +/- 4.52 and 43.09 +/- 4.18, respectively, all P <0. 01, and the average coronary blood flow increased from TIMI grade 1.75 +/- 0.42 to grade 2.70 +/- 0.45 (t = 0. 34, P < 0.05). (2) The diameter of middle segment of reopened coronary artery slightly increased from 3.2 +/- 0.3 mm to 3.3 +/- 0.4 mm 3 min after anisodamine injection, but without statistical significance (P >0. 05). (3) Successive monitoring at 10 min after anisodamine injection showed that all the parameters, including intra-coronary pressure, peripheral blood pressure, P-R interval, Q-T interval and QRS duration were not changed significantly (P > 0.05), only the heart rate increased for 15-19 beats/min, but did not induce tachycardia or other malignant arrhythmia. CONCLUSION: Intra-coronary administration of anisodamine 500 microg could improve the post-PCI slow-reflow phenomenon, it is safe and convenient, and may be taken as an effective approach for treatment of the illness.

Solasodine glycoalkaloids: a novel topical therapy for basal cell carcinoma. A double-blind, randomized, placebo-controlled, parallel group, multicenter study.

OBJECTIVE: To assess the safety and efficacy of a 0.005% mixture of solasodine glycosides (Zycure) in the treatment of basal cell carcinoma. Design Double-blind, randomized, and vehicle-controlled, parallel group study. SETTING: Ten centers in the United Kingdom. Participants Male, n = 50; female, n = 44; age range, 32-95 years (Table 1). INTERVENTION: Ninety-four patients were randomized on a 2 : 1 ratio (n = 62, Zycure; n = 32, vehicle). Histologically confirmed lesions were treated double blinded, twice daily under occlusion with Zycure or vehicle for 8 weeks. Patients were reviewed fortnightly for adverse effects and overall response. Successfully treated patients were followed up at six-month intervals for a year. MAIN OUTCOME MEASURES: The primary efficacy endpoint was histologically confirmed clearance of the basal cell carcinoma (2-mm punch biopsy) at the end of 8-week treatment. RESULTS: Efficacy (intention-to-treat population) at 8 weeks was 66% (41/62) in the Zycure group, compared to 25% (8/32) in the vehicle group (P < 0.001; Cochran-Mantel-Haenszel test). Ninety percent (37/41) of the Zycure group completed follow-up at six-month intervals for 1 year, of whom 78% (29/37) had no recurrence. There were no major treatment-related adverse effects, although 10 patients in Zycure group did not complete the treatment protocol for various reasons. CONCLUSION: We conclude that the solasodine glycoside cream Zycure is a safe therapy for basal cell carcinoma, with a cure rate of 66% at 8 weeks and 78% at 1 year follow-up.

[The effect of retrobulbar injection with anisodamine on ocular blood velocity in anterior ischemic optic neuropathy].

OBJECTIVE: To study the effect of retrobulbar injection with anisodamine on ocular blood velocity in anterior ischemic optic neuropathy (AION). METHODS: 15 minutes before injection, 15 minutes and 1 hour after injection, the blood flow velocity in 39 cases (39 eyes) diagnosed as AION was measured and analyzed by CDI, timed average maximum velocity, peak systolic velocity, end diastolic velocity, resistance index and pulsatility index of OA, CRA and PCA were recorded. RESULTS: Compared with the normal eyes, each parameter of SPCA was statistically significant. 15 minutes and 1 hour after post ocular injection of anisodamine, every parameter examined in the experiment was increased except resistance index compared with pre-injection (P < 0.01). CONCLUSIONS: retrobulbar injection with anisodamine can effectively improve flow velocity of nasal and tempo short posterior ciliary artery and central retinal artery.

The prophylactic and therapeutic effects of cholinolytics on perfluoroisobutylene inhalation induced acute lung injury.

Perfluoroisobutylene (PFIB) is a kind of fluoro-olefin that is ten times more toxic than phosgene. The mechanisms of the acute lung injury (ALI) induced by PFIB inhalation remain unclear. To find possible pharmacological interventions, mice and rats were exposed to PFIB, and the prophylactic or therapeutic effects of 3-quinuclidinyl benzilate (QNB) and anisodamine were studied and confirmed. It was observed that the wet lung/body weight and the dry lung/body weight ratios at 24 h after PFIB exposure (130 mg/m(3) for 5 min) were significantly decreased when a single dose of QNB (5 mg/kg) was administered intraperitoneally either 30 min before exposure or 10 h after exposure. Anisodamine was without any prophylactic or therapeutic effects at single doses below 30 mg/kg. The effects of QNB against PFIB inhalation induced ALI were well evidenced by the significantly decreased mice mortality at 72 h, the total protein concentration in bronchoalveolar lavage fluid at 24 h after the PFIB exposure, as well as the ultrastructural observations. The analysis of the time courses of lung sulfhydryl concentration, myeloperoxidase (MPO) activity and hemorheology assay showed that the toxicity of PFIB may be due to consumption of lung protein sulfhydryl, influx of polymorphonuclear leukocytes (PMNs) into the lung, and increased peripheral blood viscosity at a low shear rate, all of which were partially blocked by QNB intervention except for PMN influx. The results suggest that cholinolytics might have prophylactic and therapeutic roles in PFIB inhalation induced ALI.

Toxicological evaluations of long-term consumption of Solanum lycocarpum St. Hill fruits in male and female adult rats.

Solanum lycocarpum St. Hill is a common plant in the Brazilian savanna. This plant contains an alkaloid with stereospecific configuration to the synthesis of steroid hormones. Because the plant may be consumed long-term, the present study was undertaken to determine the possible toxic effects of S. lycocarpum fruit ingestion (3% added to the diet) on male (60 days of administration) and female (37 days) adult rats. Few significant differences in body weight and consumption of food and water, no significant differences in male and female weight gain or estrous cycle were detected. Female treated rats showed a significant reduction in uterus and liver weights; however, no significant differences were observed in other organ (adrenal, liver, seminal vesicle, testicle and ovary) weights in either sex. Additionally blood enzymes and proteins evaluated were not affected by treatment with 3% S. lycocarpum added to the diet. The present data, however, show sex-related differences in S. lycocarpum toxicity. Thus, other studies have to be conducted to better investigate female toxicity and other toxic effects of higher levels of exposure to this plant.

Assessment of the perinatal effects of maternal ingestion of Solanum malacoxylon in rats.

A perinatal study was performed to verify the toxic effects of Solanum malacoxylon, which contains a glycoside conjugated to Vitamin D(3). In the gestational study, female rats received S. malacoxylon leaves in the diet at 0, 0.1, 0.2, 0.5, and 1% from days 6 to 21 of pregnancy. At 21 days of gestation, blood samples were taken from the dams for evaluation of serum Ca and P. A laparotomy was performed and the rats were examined for standard parameters of reproductive performance. Fetuses were examined for skeletal changes and histopathologic evaluation. In the second trial, dams were fed diets containing 0 or 0.1% S. malacoxylon leaves during the gestation and lactation periods. After weaning, all animals were euthanized and biochemical and histopathologic evaluations were performed. The biochemical evaluation showed increase in Ca and P levels in females from all experimental groups; however, this effect did not occurred in a dose-related manner. Pups from dams exposed during gestation and lactationi also showed increased Ca and P levels. Fetal data suggested a delay of fetal development manifested by decreased body weight and skeletal alterations. There was also a reduction in live fetuses. Histopathologic study revealed alterations of the soft tissue in litters from dams given 1% dietary S. malacoxylon during pregnancy and 0.1% during pregnancy and lactation. These findings support our hypothesis that Vitamin D(3) glycoside crosses the placenta and suggests milk transfer of this substance.