Small intestine relative weight and histological sections stained with HE revealing chronic enteritis in Wistar rats. 10x magnification. (A) Small intestine relative weight in the studied groups. (B) G1: HGLI diet + water by gavage (n = 5). (C) G2: standard diet + water by gavage (n = 5). (D) Group 3: CE (12.5 mg/Kg in weight) and HGLI diet (n = 5). (E) Group 4: EPG (50 mg/Kg in weight) and HGLI diet (n = 5). CE: crude carotenoid extract from Cantaloupe melon (Cucumis melo L.). EPG: crude carotenoid extract from Cantaloupe melon nanoencapsulated in porcine gelatin. HGLI: diet with a high glycemic index and high glycemic load. ANOVA and Tukey's post-test were used to compare the studied groups (p <0.05).

Stomachs relative weight and histopathological sections stained in HE revealing aspects of normality in Wistar rats. 4x magnification. (A) Stomachs relative weight in the groups studied. (B) G1: HGLI diet + water by gavage (n = 5). (C) G2: standard diet + water by gavage (n = 5). (D) Group 3: CE (12.5 mg/Kg in weight) and HGLI diet (n = 5). (E) Group 4: EPG (50 mg/Kg in weight) and HGLI diet (n = 5). CE: crude carotenoid extract from Cantaloupe melon (Cucumis melo L.). EPG: crude carotenoid extract from Cantaloupe melon nanoencapsulated in porcine gelatin. HGLI: diet with a high glycemic index and high glycemic load. ANOVA and Tukey's post-test were used to compare the studied groups (p <0.05).

Kidneys relative weight and renal histological sections stained with HE revealing inflammatory infiltrate in Wistar rats. 40x magnification. (A) Kidney relative weight of the studied groups. (B) G1: HGLI diet + water by gavage (n = 5). (C) G2: standard diet + water by gavage (n = 5). (D) Group 3: CE (12.5 mg/Kg in weight) and HGLI diet (n = 5). (E) Group 4: EPG (50 mg/Kg in weight) and HGLI diet (n = 5). CE: crude carotenoid extract from Cantaloupe melon (Cucumis melo L.). EPG: crude carotenoid extract from Cantaloupe melon nanoencapsulated in porcine gelatin. HGLI: diet with a high glycemic index and high glycemic load. ANOVA and Tukey's post-test were used to compare the studied groups (p <0.05).

Toxicity of the bioactive dose of EPG (50 mg/Kg of weight) under hematological parameters in Wistar rats. G1: HGLI diet + water by gavage (n = 5). G2: standard diet + water by gavage (n = 5). G3: crude carotenoid extract (12.5 mg/Kg of weight) and HGLI diet (n = 5). G4: EPG (50 mg/Kg of weight) and HGLI diet (n = 5). CE: crude carotenoid extract from Cantaloupe melon (Cucumis melo L.). EPG: crude carotenoid extract from Cantaloupe melon nanoencapsulated in porcine gelatin. HGLI: diet with a high glycemic index and high glycemic load. The statistical difference between the groups was assessed using the Kruskal-Wallis and Dunn's post-test for non-parametric variables, according to the Kolmogorov-Smirnov normality test, with p <0.05. Moreover, through ANOVA (p <0.05) and Tukey's post-test for parametric variables.

Toxicity of the bioactive dose of EPG (50 mg/Kg in weight) under renal and protein biochemical parameters in Wistar rats. G1: HGLI + water per gavage (n = 5). G2: standard diet + water per gavage (n = 5). G3: crude carotenoid extract (12.5 mg/Kg in weight) and HGLI diet (n = 5). G4: EPG (50 mg/Kg in weight) and HGLI diet (n = 5). CE: crude carotenoid extract from Cantaloupe melon (Cucumis melo L.). EPG: crude carotenoid extract from Cantaloupe melon nanoencapsulated in porcine gelatin. HGLI: diet with a high glycemic index and high glycemic load. ANOVA and Tukey's post-test were used to compare the studied groups (p < 0,05).

Spleens relative weight and histopathological sections stained in HE revealing aspects of normality in Wistar rats. (A) Relative spleen weight of the studied groups. (B) G1: HGLI diet + water by gavage (n = 5). (C) G2: standard diet + water by gavage (n = 5). (D) Group 3: CE (12.5 mg/Kg in weight) and HGLI diet (n = 5). (E) Group 4: EPG (50 mg/Kg in weight) and HGLI diet (n = 5). CE: crude carotenoid extract from Cantaloupe melon (Cucumis melo L.). EPG: crude carotenoid extract from Cantaloupe melon nanoencapsulated in porcine gelatin. HGLI: diet with a high glycemic index and high glycemic load. ANOVA and Tukey's post-test were used to compare the studied groups (p <0.05).

Relative liver weight and liver histological sections stained with H&E revealing acute hepatitis in Wistar rats. 40x magnification. (A) Relative liver weight of the groups studied. (B) G1: HGLI diet + water by gavage (n = 5). (C) G2: standard diet + water by gavage (n = 5). (D) Group 3: crude carotenoid extract (12.5 mg/Kg in weight) and HGLI diet (n = 5). (E) Group 4: EPG (50 mg/Kg of weight) and HGLI diet (n = 5). CE: crude carotenoid extract from Cantaloupe melon (Cucumis melo L.). EPG: crude carotenoid extract from Cantaloupe melon nanoencapsulated in porcine gelatin. HGLI: diet with a high glycemic index and high glycemic load. ANOVA and Tukey's post-test were used to compare the studied groups (p <0.05).

Toxicity of the bioactive dose of EPG (50 mg/Kg of weight) under parameters of fasting blood glucose and lipid profile in Wistar rats. G1: HGLI diet + water by gavage (n = 5). G2: standard diet + water per gavage (n = 5). G3: crude carotenoid extract (12.5 mg/Kg in weight) and HGLI diet (n = 5). G4: EPG (50 mg/Kg in weight) and HGLI diet (n = 5). CE: crude carotenoid extract from Cantaloupe melon (Cucumis melo L.). EPG: crude carotenoid extract from Cantaloupe melon nanoencapsulated in porcine gelatin. HGLI: diet with a high glycemic index and high glycemic load. The statistical difference between the groups was assessed using ANOVA (p <0.05) and Tukey's post-test.

Toxicity of the bioactive dose of EPG (50 mg/Kg in weight) under biochemical parameters in Wistar rats. G1: HGLI + water per gavage (n = 5). G2: standard diet + water per gavage (n = 5). G3: crude carotenoid extract (12.5 mg/Kg in weight) and HGLI diet (n = 5). G4: EPG (50 mg/Kg in weight) and HGLI diet (n = 5). CE: crude carotenoid extract from Cantaloupe melon (Cucumis melo L.). EPG: crude carotenoid extract from Cantaloupe melon nanoencapsulated in porcine gelatin. HGLI: diet with a high glycemic index and high glycemic load. The Kruskal-Wallis tests and Dunn's post-test was used to compare the groups for non-parametric variables, according to the Kolmogorov-Smirnov normality test, with p <0.05. ANOVA and Tukey's post-test were used to compare the studied groups for the parametric variables (p <0.05).

This study evaluated the safety and bioactive potential of nanoparticles containing carotenoids from Cantaloupe melon crude extract and porcine gelatin (EPG) in male obese Wistar rats. Animals were fed with a high glycemic index and high glycemic load (HGLI) diet for 17 days, and treated for ten days with 1) HGLI diet, 2) Standard diet, 3) HGLI diet + EPG (50 mg/Kg) or 4) HGLI diet + crude carotenoid extract (CE) (12.5 mg/Kg). Signs of general toxicity were investigated, considering body weight, food intake, hematological, and biochemical parameters. The relative weight, morphology, and histopathology of the liver, small intestine, kidneys, stomach, and spleen were also evaluated. The biochemical parameters indicated the low toxicity of EPG. Acute hepatitis was observed in the livers of all animals, but those treated with CE and EPG presented tissue better appearance. For the small intestine, chronic enteritis was observed in all animals, with considerable preservation in the villi and intestinal glands of animals treated with EPG. The results suggest EPG is safe for application and presents a bioactive effect, possibly related to the anti-inflammatory potential, demonstrating the safety for use in future preclinical and clinical studies.