Effects of dexpanthenol on 5-fluorouraci-induced nephrotoxicity, hepatotoxicity, and intestinal mucositis in rats: a clinical, biochemical, and pathological study

Şeyma Taştemur; Mehmet Ekĭcĭ; Ali Sefa Mendĭl; Mustafa Özkaraca; Hilmi Ataseven

doi:10.2478/abm-2025-0006

Figures & Tables

Experimental design. 5-FU, 5-fluorouracil; 8-OHdG, 8-hydroxyguanosine; ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; BUN, blood urea nitrogen; COX-2, cyclooxygenase-2; DXP, dexpanthenol; LDH, lactate dehydrogenase; iNOS, inducible nitric oxide synthase; NF-κB, nuclear factor kappa B.

(A) body weight changes, (B) food intake changes, and (C) diarrhea score changes. *P < 0.05, **P < 0.01, and ***P < 0.001 are significant 5-FU group compared with control group; #P < 0.05, ##<I>P < 0.01, and ###P < 0.001 are significant 5-FU+DXP500 group compared with 5-FU group; ϕP < 0.05, ϕϕP < 0.01, and ϕϕϕP < 0.001 are significant 5-FU+DXP1000 group compared with 5-FU group according to one-way ANOVA post hoc Tukey test in Graph Pad Prism 8.0.1 software. 5-FU, 5-fluorouracil; DXP, dexpanthenol.

Liver and renal biochemical analysis results. AST (a), ALT (b), ALP (c), total bilirubin (d), direct bilirubin (e), LDH (f), BUN (g), creatinine (h), uric acid (i), total protein (j), and albumin (k) level changes in groups. *P < 0.05, **P < 0.01, and ***P < 0.001 are significant 5-FU group compared with the control group; #P < 0.05, ##P < 0.01, and ###P < 0.001 are significant 5-FU+DXP500 and 5-FU+DXP1000 groups compared with 5-FU group according to one-way ANOVA post hoc Tukey test in Graph Pad Prism 8.0.1 software. 5-FU, 5-fluorouracil; ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; BUN, blood urea nitrogen; DXP, dexpanthenol; LDH, lactate dehydrogenase.

Images of histopathologic findings in H&E stained liver tissues. (A, B) Control group: Normal histologic appearance. (C, D) 5-FU group: Severe hepatocyte pyknosis (arrow), mononuclear cell infiltration around the bile ducts (□), and mild hepatocyte degeneration (arrowhead). (E, F) 5-FU+DXP500 group: Mononuclear cell infiltrations around the bile ducts (□) with moderate hepatocyte pyknosis (arrow) and mild hepatocyte degeneration (arrowhead). (G, H) 5-FU+DXP1000 group: Mild hepatocyte pyknosis (arrow), mononuclear cell infiltrations around the bile ducts (□), and hepatocyte degeneration (arrowhead). 5-FU, 5-fluorouracil; DXP, dexpanthenol.

Images of histopathologic findings in H&E stained renal tissues. (A, B) Control group: Normal histologic appearance. (C, D) 5-FU group: Moderate mononuclear cell infiltration in interstitial areas (arrowhead) and degenerative tubules (□). (E, F) 5-FU+DXP500 group and (G, H) 5-FU+DXP1000 group: Mild mononuclear cell infiltrations (arrowhead) and degenerative tubules (□) in interstitial areas. 5-FU, 5-fluorouracil; DXP, dexpanthenol.

Images of histopathologic findings in H&E stained jejunum and colon tissues. (A, B) Control group: Normal histologic appearance. (C, D) 5-FU group: Moderate hyperemia (arrowhead), mononuclear cell infiltrations (□), moderate hemorrhage (arrow), and mild mononuclear cell infiltrations (□) in the jejunum. (E, F) 5-FU+DXP500 group and (G, H) 5-FU+DXP1000 group: Mild hyperemia (arrowhead), mononuclear cell infiltrations (□), and hemorrhage (arrow) in the jejunum and colon. 5-FU, 5-fluorouracil; DXP, dexpanthenol.

Images of immunohistochemical findings in liver tissues. Severe immunopositivity in the 5-FU group, moderate immunopositivity in the 5-FU+DXP500 group, and mild immunopositivity in the 5-FU+DXP1000 group for 8-OHdG, NF-κB, COX-2, and iNOS (arrows), respectively. 5-FU, 5-fluorouracil; 8-OHdG, 8-hydroxyguanosine; COX-2, cyclooxygenase-2; DXP, dexpanthenol; iNOS, inducible nitric oxide synthase; NF-κB, nuclear factor kappa B.

Images of immunohistochemical findings in renal tissues. In the control group, there was mild immunopositivity for COX-2 and iNOS, while in the 5-FU group, there was mild immunopositivity for 8-OHdG and NF-κB, and severe immunopositivity for COX-2 and iNOS. In the 5-FU+DXP500 and 5-FU+DXP1000 groups, there was moderate immunopositivity for COX-2 and iNOS (arrows). 5-FU, 5-fluorouracil; 8-OHdG, 8-hydroxyguanosine; COX-2, cyclooxygenase-2; DXP, dexpanthenol; iNOS, inducible nitric oxide synthase; NF-κB, nuclear factor kappa B.

Images of immunohistochemical findings in jejunum tissues. Mild COX-2 and iNOS immunopositivity in the control group, moderate 8-OHdG, severe NF-κB, COX-2, and very severe iNOS immunopositivity in the 5-FU group, mild 8-OHdG, moderate NF-κB, COX-2, and severe iNOS immunopositivity in the 5-FU+DXP500 and 5-FU+DXP100 groups (arrows: immunopositivity in the villi, arrowheads: immunopositivity in the lamina epithelialis). 5-FU, 5-fluorouracil; 8-OHdG, 8-hydroxyguanosine; COX-2, cyclooxygenase-2; DXP, dexpanthenol; iNOS, inducible nitric oxide synthase; NF-κB, nuclear factor kappa B.

Images of immunohistochemical findings in colonic tissues. Mild 8-OHdG, COX-2 and iNOS immunopositivity in the control group, severe 8-OHdG, moderate NF-κB, severe COX-2, and moderate iNOS immunopositivity in the 5-FU group, moderate 8-OHdG, mild NF-κB, moderate COX-2, and mild iNOS immunopositivity in the 5-FU+DXP500 and 5-FU+DXP100 groups (arrows: immunopositivity in the mucosa, arrowheads: immunopositivity in the lamina epithelialis). 5-FU, 5-fluorouracil; 8-OHdG, 8-hydroxyguanosine; COX-2, cyclooxygenase-2; DXP, dexpanthenol; iNOS, inducible nitric oxide synthase; NF-κB, nuclear factor kappa B.

Histopathological scoring

Liver	Degenerative, necrotic-pyknotic hepatocytes in microscope fields;
	Absent (−), 1–5 < (+, mild), 6–9 (++, moderate), 9> (+++, severe)
	Infiltrative mononuclear cell count in microscope fields;
	Absent (−), 2–10 < (+, mild), 11–20 (++, moderate), 21> (+++, severe)

Kidney	Degenerative tubule in microscope fields;
	Absent (−), 1–5 < (+, mild), 6–10 (++, moderate), 11> (+++, severe)
	Mononuclear cell focus in microscope fields;
	Absent (−), 1 (+, mild), 2 (++, moderate), 3> (+++, severe)

Jejenum and colon	Hypremia focus in microscope fields;
	Absent (−), 1–5 (+, mild), 6–10 (++, moderate), 11> (+++, severe)
	Area of the villus (%) in microscope fields;
	Absent (−), 25 < (+, mild), 26–50 (++, moderate), 51> (+++, severe)

Histopathological findings and statistical analysis of immunohistochemical staining in liver, renal, jejunum, and colon tissues

a) Histopathological findings and statistical analysis of immunohistochemical staining in liver tissues

Groups	Mononuclear cell infiltration	Pyknosis in hepatocytes	Degeneration in hepatocytes	8-OHdG	NF-κB	COX-2	iNOS

Control	0.16 ± 0.40^†	0.33 ± 0.51^†	0.33 ± 0.51^†	0.00 ± 0.00^†	0.00 ± 0.00^†	0.00 ± 0.00^†	0.00 ± 0.00^†
5-FU	2.83 ± 0.40^‡	2.66 ± 0.51^‡	1.00 ± 0.00^‡	2.66 ± 0.51^†	2.83 ± 0.40^‡	1.83 ± 0.40^‡	2.66 ± 0.51^‡
5-FU+DXP500	2.00 ± 0.00^§	1.83 ± 0.40^§	1.00 ± 0.00^‡	1.66 ± 0.51^§	1.83 ± 0.40^§	1.66 ± 0.51^‡	1.66 ± 0.51^§
5-FU+DXP1000	1.00 ± 0.00^‖	1.33 ± 0.51^‖	1.16 ± 0.40^‡	0.83 ± 0.40^‖	1.00 ± 0.00^‖	0.66 ± 0.51^‖	0.66 ± 0.51^‖

b) Histopathological findings and statistical analysis of immunohistochemical staining in renal tissues

Groups	Mononuclear cell infiltration	Tubular degeneration		8-OHdG	NF-κB	COX-2	iNOS

Control	0.16 ± 0.40^†	0.33 ± 0.51^†		0.00 ± 0.00^†	0.00 ± 0.00^†	0.83 ± 0.40^†	0.83 ± 0.40^†
5-FU	1.83 ± 0.40^‡	2.00 ± 0.00^‡		0.83 ± 0.40^‡	0.66 ± 0.51^‡	2.83 ± 0.40^‡	2.66 ± 0.51^‡
5-FU+DXP500	0.83 ± 0.40^§	1.00 ± 0.00^§		0.00 ± 0.00^†	0.00 ± 0.00^†	1.66 ± 0.51^§	1.83 ± 0.40^§
5-FU+DXP1000	1.00 ± 0.00^§	0.83 ± 0.40^§		0.00 ± 0.00^†	0.00 ± 0.00^†	1.83 ± 0.40^§	1.83 ± 0.40^§

c) Histopathological findings and statistical analysis of immunohistochemical staining in jejunum tissues

Groups	Mononuclear cell infiltration	Villous hyperemia		8-OhdG	NF-κB	COX-2	iNOS

Control	0.00 ± 0.00^†	0.00 ± 0.00^†		0.33 ± 0.51^†	0.33 ± 0.51^†	1.00 ± 0.00^†	1.16 ± 0.40^†
5-FU	2.16 ± 0.40^‡	1.66 ± 0.51^‡		1.66 ± 0.51^‡	2.66 ± 0.51^‡	2.83 ± 0.40^‡	3.66 ± 0.51^‡
5-FU+DXP500	1.00 ± 0.00^§	0.83 ± 0.40^§		0.66 ± 0.51^§	1.83 ± 0.40^§	1.83 ± 0.40^§	2.83 ± 0.40^§
5-FU+DXP1000	1.00 ± 0.00^§	0.66 ± 0.51^§		0.66 ± 0.51^§	1.66 ± 0.51^§	2.00 ± 0.00^§	1.66 ± 0.51^§

d) Histopathological findings and statistical analysis of immunohistochemical staining in colonic tissues

Groups	Mononuclear cell infiltration	Hemorrhage		8-OhdG	NF-κB	COX-2	iNOS

Control	0.00 ± 0.00^†	0.00 ± 0.00^†		0.66 ± 0.51^†	0.16 ± 0.40^†	1.16 ± 0.40^†	0.66 ± 0.40^†
5-FU	0.66 ± 0.51^‡	1.66 ± 0.51^‡		2.83 ± 0.40^‡	1.66 ± 0.51^‡	3.00 ± 0.00^‡	1.66 ± 0.51^‡
5-FU+DXP500	0.00 ± 0.00^†	0.66 ± 0.51^§		2.00 ± 0.00^§	0.66 ± 0.51^§	2.16 ± 0.40^§	0.66 ± 0.51^†
5-FU+DXP1000	0.16 ± 0.40^†	0.66 ± 0.51^§		2.16 ± 0.40^§	0.66 ± 0.51^§	2.16 ± 0.40^§	0.83 ± 0.40^†

Immunohistochemical scoring

Liver	Immunopositivity cells count
	Absent (−), 5 < (+, mild), 5–10 (++, moderate), 10> (+++, severe)

Kidney	Immunopositivity tubules count
	Absent (−), 5 < (+, mild), 5–10 (++, moderate), 10> (+++, severe)

Jejenum and colon	Area of the villus (%)
	Absent (−), 5 < (+, mild), 5–15 (++, moderate), 15–30> (+++, severe)
	30%> (++++, very severe)

Effects of dexpanthenol on 5-fluorouraci-induced nephrotoxicity, hepatotoxicity, and intestinal mucositis in rats: a clinical, biochemical, and pathological study

Figures & Tables

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Histopathological scoring

Histopathological findings and statistical analysis of immunohistochemical staining in liver, renal, jejunum, and colon tissues

Immunohistochemical scoring

Paradigm

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